Multi-ethnic genome-wide association study for atrial fibrillation

• Type of Material: Article
• Authors: Carolina Roselli, Broad Institute of MIT and Harvard; Mark D. Chaffin, Broad Institute of MIT and Harvard; Lu-Chen Weng, Broad Institute of MIT and Harvard; Stefanie Aeschbacher, University Hospital Basel; Gustav Ahlberg, Copenhagen University Hospital; Christine M. Albert, Brigham & Womens Hospital; Peter Almgren, Lund University; Alvaro Alonso, Emory University; Christopher D. Anderson, Broad Institute of MIT and Harvard; Krishna G. Aragam, Broad Institute of MIT and Harvard; Dan E. Arking, Johns Hopkins University; John Barnard, Cleveland Clinic; Traci M. Bartz, University of Washington; Emelia J. Benjamin, National Heart Lung and Blood Institute; Nathan A. Bihlmeyer, Johns Hopkins University; Joshua C. Bis, University of Washington; Heather Bloom, Emory University; Eric Boerwinkle, Baylor College of Medicine; Erwin B. Bottinger, Icahn School of Medicine at Mount Sinai; Jennifer A. Brody, University of Washington
• Language: English
• Date: 2018-09-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1038/s41588-018-0133-9
• Title of Journal or Parent Work: Nature Genetics
• ISSN: 1061-4036
• Volume: 50
• Issue: 9
• Start Page: 1225
• End Page: +
• Keywords: GWAS CATALOG; POLYMORPHIC VENTRICULAR-TACHYCARDIA; Life Sciences & Biomedicine; Science & Technology; CARDIAC CONDUCTION; COMPONENTS-ANALYSIS; MUTATIONS; GENE; DISEASE; VARIANTS; Genetics & Heredity; LOCI; IDENTIFICATION
• Research Categories: Biology, Genetics

Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.