Genome-wide association study of 1 million people identifies 111 loci for atrial fibrillation
Author:
Nielsen Jonas B.ORCID, Thorolfsdottir Rosa B., Fritsche Lars G.ORCID, Zhou WeiORCID, Skov Morten W., Graham Sarah E., Herron Todd J., McCarthy Shane, Schmidt Ellen M., Sveinbjornsson Gardar, Surakka Ida, Mathis Michael R., Yamazaki Masatoshi, Crawford Ryan D., Gabrielsen Maiken E., Skogholt Anne Heidi, Holmen Oddgeir L., Lin Maoxuan, Wolford Brooke N.ORCID, Dey Rounak, Dalen Håvard, Sulem Patrick, Chung Jonathan H., Backman Joshua D., Arnar David O., Thorsteinsdottir Unnur, Baras Aris, O’Dushlaine Colm, Holst Anders G., Wen Xiaoquan, Hornsby Whitney, Dewey Frederick E., Boehnke Michael, Kheterpal Sachin, Lee SeunggeunORCID, Kang Hyun M., Holm Hilma, Kitzman Jacob, Shavit Jordan A., Jalife José, Brummett Chad M., Teslovich Tanya M., Carey David J., Gudbjartsson Daniel F., Stefansson Kari, Abecasis Goncalo R., Hveem Kristian, Willer Cristen J.ORCID
Abstract
SummaryTo understand the genetic variation underlying atrial fibrillation (AF), the most common cardiac arrhythmia, we performed a genome-wide association study (GWAS) of > 1 million people, including 60,620 AF cases and 970,216 controls. We identified 163 independent risk variants at 111 loci and prioritized 165 candidate genes likely to be involved in AF. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans or mice (MYH6, NKX2-5, PITX2, TBC1D32, TBX5),1,2 or near genes important for striated muscle function and integrity (e.g. MYH7, PKP2, SSPN, SGCA). Experiments in rabbits with heart failure and left atrial dilation identified a heterogeneous distributed molecular switch from MYH6 to MYH7 in the left atrium, which resulted in contractile and functional heterogeneity and may predispose to initiation and maintenance of atrial arrhythmia.
Publisher
Cold Spring Harbor Laboratory
Reference50 articles.
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