/ en /news/study-finds-youth-onset-diabetes-genetically-distinct-form-disorder <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Fri, 16 Feb 2024 15:00:00 +0000 chenders@broadinstitute.org 5556451 at /news/count-me-patient-partnered-research-launches-new-project-pediatric-hepatocellular-carcinoma <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Tue, 28 Nov 2023 19:07:09 +0000 kzusi@broadinstitute.org 5556146 at /news/lung-cancers-molecular-features-shed-light-immunotherapy-response <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Tue, 18 Apr 2023 14:51:33 +0000 kzusi@broadinstitute.org 1282071 at /news/launch-merkin-prize-biomedical-technology <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Tue, 29 Nov 2022 15:48:53 +0000 kzusi@broadinstitute.org 1269891 at /news/first-large-genetic-study-bipolar-disorder-asian-populations-launches <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Mon, 31 Oct 2022 16:53:52 +0000 aviveros@broadinstitute.org 1238511 at /news/rna-sensing-system-measures-and-controls-protein-expression-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Thu, 27 Oct 2022 14:56:30 +0000 adicorat 1213391 at /news/study-explores-effects-changes-non-coding-genome-neurodevelopmental-disorders <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Mon, 24 Oct 2022 13:03:40 +0000 aviveros@broadinstitute.org 1230456 at /news/largest-genome-wide-association-study-ever-uncovers-nearly-all-genetic-variants-linked-height <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Wed, 12 Oct 2022 15:02:54 +0000 adicorat 1167101 at /news/brain-organoids-replicate-key-events-human-brain-development <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Thu, 29 Sep 2022 15:01:07 +0000 adicorat 1203406 at /news/researchers-develop-strategy-precisely-target-subtypes-key-protein <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Claire Hendershot</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" class="datetime">February 16, 2024</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Study finds youth-onset diabetes is a genetically distinct form of the disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers suggest diabetes exists in multiple forms on a spectrum of varying genetic factors and symptoms.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Claire Hendershot </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2024-02-16T10:00:00-05:00" title="Friday, February 16, 2024 - 10:00" class="datetime">February 16, 2024</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=bujGwyGh 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=i1y0h_VJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=nJaDkXwR 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=5amqC94B 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"> <img loading="eager" src="/files/styles/multiple_ct_header_phone/public/longstory/0224%20News%20Story%20Diabetes_v01.png?h=ae0fde30&amp;itok=GMcFxPRW" width="499" height="294" alt="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." title="Youth-onset type 2 diabetes lies on a genetic spectrum between rare forms of diabetes and adult-onset diabetes." typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__description"> Image by Ricardo Job-Reese, ӳ����ý Communications. </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/696/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons__button share-facebook" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/696/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons__button share-x" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&amp;body=/taxonomy/term/696/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons__button share-email" target="_blank" rel="noopener"> <svg width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The diabetes field has long classified the disorder into genetically distinct groups, including type 1 and type 2. However, new genetics research focused on a form of type 2 diabetes (T2D) that is becoming more common in adolescents suggests a more complicated picture.&nbsp;<br> &nbsp;<br> Researchers at the ӳ����ý of MIT and Harvard, Boston Children's Hospital, and Harvard Medical School analyzed DNA from more than 3,000 T2D participants between 12 and 18-years-old and nearly 9,800 adult controls, more than three-quarters of whom were of African American or Hispanic ancestry. They found that youth-onset T2D is a genetically intermediate form of the disorder that lies on a spectrum between adult-onset T2D and rare forms of the disorder caused by a single gene. &nbsp;</p> <p>Adult-onset T2D is influenced by thousands of common genetic variants, whereas the rare genetic forms, known as monogenic diabetes, are caused by a single variant. However, in a recent <a href="https://www.nature.com/articles/s42255-023-00970-0#"><em>Nature Metabolism</em></a> paper, the researchers showed that youth-onset T2D shared some of the same genetic features as both forms, carrying both common and rare genetic variants. Moreover, these individuals harbored more of these variants than people with adult-onset T2D, suggesting that genetics has a larger role in causing youth-onset T2D than in the adult-onset form.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related News</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=x4UcPenS 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=ca4DFv52 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=TkGdE0Ez 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/healthy%20adipocytes%20with%20fat%20deposits%20743x503.jpg?h=ae0fde30&amp;itok=pQiUMeNN" width="220" height="186" alt="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." title="Color fluorescence microscope image of fat cells, aka adipocytes, with functional COBLL1. The cytoskeleton is dyed yellow, lipids are dyed green, cell nuclei are dyed blue. Many green fat deposits are visible." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/study-finds-how-genetic-variant-raises-diabetes-risk-through-unexpected-mechanism" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Study finds how a genetic variant raises diabetes risk through an unexpected mechanism</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The work also revealed that the specific mix of different types of variants a given individual carried correlated with their particular set of symptoms. For example, those with more common variants showed more symptoms of adult-onset T2D, such as high insulin levels.</p> <p>The findings challenge current thinking about T2D, by suggesting that there is more genetic overlap between the different forms of diabetes than previously thought.&nbsp;</p> <p>“The way that clinicians subdivide diabetes patients now is based on symptoms, but in this study, the frequency of genetic risk factors seems to vary among patients with youth-onset T2D,” said <a href="/bios/jason-flannick">Jason Flannick</a>, ӳ����ý associate member and assistant professor at Boston Children’s Hospital and Harvard Medical School. “We didn’t expect that frequency of genetic variants would correlate with clinical presentation, but that amazingly seems to be what we’re seeing.”</p> <p>According to the study's first author, Soo Heon Kwak, a visiting scientist at ӳ����ý in Flannick’s lab and now a clinician based at Seoul National University Hospital in Korea, the study's findings challenge our current way of thinking about T2D and other complex diseases, which buckets patients into black-and-white symptomatic categories.</p> <p>“Before this study, there was no clear view on the genetic architecture of youth-onset T2D. This provides a view of the overall genetics of diabetes,” said Kwak.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Flagging risk factors</h2> <p>Disease-causing genetic variants are generally classified as common (appearing in more than 5 percent in the population), rare (less than 1 to 5 percent of population), or monogenic (which are able to cause disease on their own). Teasing apart the contributions of these different types of variants in youth-onset T2D risk requires genetic data from thousands of patients.</p> <p>To access such a large dataset, Kwak and Flannick turned to ProDiGY (Progress in Diabetes Genetics in Youth), a National Institutes of Health-funded research consortium that has sequenced the exomes (the protein-coding region of the genome) of thousands of adolescents with T2D and also collected common genetic variant data from many thousands of healthy adults.</p> <p>Their analyses demonstrated that the combination of common and rare genetic variants in youth-onset T2D have a greater influence on disease risk than in the adult-onset form. Youth-onset patients' common variant risk was three-fold higher, and their rare variant risk was five-fold higher.&nbsp;</p> <p>Kwak and Flannick, building upon work previously published by the ProDiGY consortium, also found that 2.4 percent of the youth-onset T2D patients had monogenic diabetes, including a significant number of patients who carried variants in <em>MC4R</em>, a gene strongly linked to monogenic obesity. They said that these cases should be screened for monogenic diabetes, which might change the types of treatments they would receive.</p> <p>“There’s a nontrivial fraction that is worth getting screened for monogenic forms of diabetes, even if they don’t exactly look like what typical monogenic cases look like,” said Flannick.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><h2>Towards precision medicine</h2> <p> Researchers have long thought that common variants are the most significant genetic risk factor for diabetes, but Kwak says that the study may change that thinking. “There’s been a long debate on the genetic architecture for T2D, and the field tends to lean toward the common variant hypothesis. But we show that there are rare variants that are important even after excluding the monogenic diabetes cases.”</p> <p>Kwak and Flannick hope that their study can inform the development of new diabetes treatments and add that their approach can be used to better understand the genetic causes of other diseases.</p> <p>“I think this could have a huge impact on other studies of complex disease with early-onset forms,” said Kwak. “There’s a lot of heterogeneity in the different forms of common disease. With this model, we can understand other conditions' genetic architecture.”&nbsp;</p> <p>&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Research Foundation of Korea, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Diabetes Association, the National Human Genome Research Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Heart, Lung, and Blood Institute, and other sources.&nbsp;</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper Cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Paper Cited: Kwak, S.H., Srinivasan, S., Chen, L. et al. <a href="https://www.nature.com/articles/s42255-023-00970-0#">Genetic architecture and biology of youth-onset type 2 diabetes</a>. <em>Nature Metabolism</em>. Online January 26, 2024. DOI: 10.1038/s42255-023-00970-0.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/metabolic-disease" hreflang="en">Metabolic Disease</a></div> <div class="field__item"><a href="/broad-tags/diabetes" hreflang="en">Diabetes</a></div> <div class="field__item"><a href="/broad-tags/news-and-media" hreflang="en">News and Media</a></div> </div> </div> </div> </div> </div> Mon, 26 Sep 2022 19:10:06 +0000 aviveros@broadinstitute.org 1202331 at