| Literature DB >> 36267918 |
Sébastien Thériault1,2, Medea Imboden3,4, Mary L Biggs5,6, Thomas R Austin7, Stefanie Aeschbacher8,9, Emmanuel Schaffner3,4, Jennifer A Brody5, Traci M Bartz5,6, Martin Risch10,11, Kirsten Grossmann10,12, Henry J Lin13, Elsayed Z Soliman14, Wendy S Post15, Lorenz Risch10,16, Jose E Krieger17, Alexandre C Pereira17, Susan R Heckbert7,18, Nona Sotoodehnia5,19, Nicole M Probst-Hensch3,4, David Conen2.
Abstract
Premature atrial contractions (PACs) are frequently observed on electrocardiograms and are associated with increased risks of atrial fibrillation (AF), stroke, and mortality. In this study, we aimed to identify genetic susceptibility loci for PAC frequency. We performed a genome-wide association study meta-analysis with PAC frequency obtained from ambulatory cardiac monitoring in 4,831 individuals of European ancestry. We identified a genome-wide significant locus at the SCN5A gene. The lead variant, rs7373862, located in an intron of SCN5A, was associated with an increase of 0.12 [95% CI 0.08-0.16] standard deviations of the normalized PAC frequency per risk allele. Among genetic variants previously associated with AF, there was a significant enrichment in concordance of effect for PAC frequency (n = 73/106, p = 5.1 × 10-5). However, several AF risk loci, including PITX2, were not associated with PAC frequency. These findings suggest the existence of both shared and distinct genetic mechanisms for PAC frequency and AF.Entities:
Keywords: Cardiovascular medicine; Clinical genetics; Genomics; Human genetics
Year: 2022 PMID： 36267918 PMCID： PMC9576575 DOI： 10.1016/j.isci.2022.105210
Source DB: PubMed Journal: iScience ISSN： 2589-0042