Key result
A genome-wide association study of over 1 million people identified 163 independent risk variants at 111 loci associated with atrial fibrillation, including 80 novel loci.
Meta-Analysis (n=1,030,836)
Yes
p-value: p=<5x10-8
A large-scale genome-wide association study identified 111 loci and 165 candidate genes associated with atrial fibrillation, highlighting genes involved in striated muscle function and structural heart defects.
Summary To 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.
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Nielsen et al. (2018) conducted a meta-analysis in Atrial fibrillation (n=1,030,836). Genetic variants vs. Controls without atrial fibrillation was evaluated on Genome-wide significant association with atrial fibrillation (p=<5x10-8). A genome-wide association study of over 1 million people identified 163 independent risk variants at 111 loci associated with atrial fibrillation, including 80 novel loci.
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