Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.
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| Abstract | Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. |
| Year of Publication | 2014
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| Journal | Am J Hum Genet
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| Volume | 94
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| Issue | 3
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| Pages | 349-60
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| Date Published | 2014 Mar 06
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| ISSN | 1537-6605
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| URL | |
| DOI | 10.1016/j.ajhg.2013.12.016
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| PubMed ID | 24560520
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| PubMed Central ID | PMC3951943
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| Grant list | SP/08/002/24118 / British Heart Foundation / United Kingdom
G9521010 / Medical Research Council / United Kingdom
PG/09/022/26739 / British Heart Foundation / United Kingdom
G0802432 / Medical Research Council / United Kingdom
FS/11/35/28871 / British Heart Foundation / United Kingdom
UL1 TR000064 / TR / NCATS NIH HHS / United States
U01 GM074492 / GM / NIGMS NIH HHS / United States
R37 AG011099 / AG / NIA NIH HHS / United States
R01 AG021917 / AG / NIA NIH HHS / United States
FS/12/33/29561 / British Heart Foundation / United Kingdom
R01 AG016592 / AG / NIA NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
PG/07/085/23349 / British Heart Foundation / United Kingdom
R01 HL074730 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
FS/14/12/30540 / British Heart Foundation / United Kingdom
FS/12/8/29377 / British Heart Foundation / United Kingdom
P30 DK072488 / DK / NIDDK NIH HHS / United States
MC_UU_12013/1 / Medical Research Council / United Kingdom
090532 / Wellcome Trust / United Kingdom
G0902313 / Medical Research Council / United Kingdom
MR/K006584/1 / Medical Research Council / United Kingdom
MR/K013351/1 / Medical Research Council / United Kingdom
MC_UU_12013/8 / Medical Research Council / United Kingdom
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