Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.

Circulation. Genomic and Precision Medicine
Honghuang LinAaron Isaacs

Abstract

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. 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. We identified 31 genetic loci that were significantly associated with PR interval after Bonferroni correction (P<1.2×10-6), 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 MYH6 (P=5.9×10-11) and SCN5A (P=1.1×10-7) were associated with PR interval. SCN5A locus also was implicated in the common variant analysis, whereas MYH6 was a novel locus. 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 ...Continue Reading

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Citations

May 20, 2020·Cardiovascular Research·Charlotte GlingeConnie R Bezzina
Aug 22, 2020·Circulation. Genomic and Precision Medicine·Lu-Chen WengSteven A Lubitz
Jan 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lara GharibehMona Nemer
Mar 22, 2021·Human Genetics·Shadi AhmadmehrabiDaniel J Rader

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