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Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

Original publication

DOI

10.1038/ng.3843

Type

Journal article

Journal

Nature genetics

Publication Date

06/2017

Volume

49

Pages

946 - 952

Addresses

Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.

Keywords

METASTROKE Consortium of the ISGC, Neurology Working Group of the CHARGE Consortium, AFGen Consortium, Humans, Atrial Fibrillation, Genetic Predisposition to Disease, Quantitative Trait Loci, African Americans, European Continental Ancestry Group, Genome-Wide Association Study, Genetic Loci