Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.
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| Abstract | BACKGROUND: Electrical conduction from the cardiac sinoatrial node to the ventricles is critical for normal heart function. Genome-wide association studies have identified more than a dozen common genetic loci that are associated with PR interval. However, it is unclear whether rare and low-frequency variants also contribute to PR interval heritability. METHODS: We performed large-scale meta-analyses of the PR interval that included 83 367 participants of European ancestry and 9436 of African ancestry. We examined both common and rare variants associated with the PR interval. RESULTS: We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (1.2×10), including 11 novel loci that have not been reported previously. Many of these loci are involved in heart morphogenesis. In gene-based analysis, we found that multiple rare variants at (=5.9×10) and (=1.1×10) were associated with PR interval. locus also was implicated in the common variant analysis, whereas was a novel locus. CONCLUSIONS: We identified common variants at 11 novel loci and rare variants within 2 gene regions that were significantly associated with PR interval. Our findings provide novel insights to the current understanding of atrioventricular conduction, which is critical for cardiac activity and an important determinant of health. |
| Year of Publication | 2018
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| Journal | Circ Genom Precis Med
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| Volume | 11
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| Issue | 5
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| Pages | e002037
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| Date Published | 2018 05
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| ISSN | 2574-8300
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| DOI | 10.1161/CIRCGEN.117.002037
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| PubMed ID | 29748316
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| PubMed Central ID | PMC5951629
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| Grant list | R01 HL139731 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
U01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
T32 HL007208 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
S10 OD020069 / OD / NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
UL1 TR001430 / TR / NCATS NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
U54 GM115428 / GM / NIGMS NIH HHS / United States
K23 HL114724 / HL / NHLBI NIH HHS / United States
R01 HL111089 / HL / NHLBI NIH HHS / United States
R01 HL116747 / HL / NHLBI NIH HHS / United States
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