Multi-ethnic genome-wide association study for atrial fibrillation

Research output: Contribution to journalArticle

Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and 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.

Details

Authors
  • Carolina Roselli
  • Mark D. Chaffin
  • Lu Chen Weng
  • Stefanie Aeschbacher
  • Gustav Ahlberg
  • Christine M. Albert
  • Peter Almgren
  • Alvaro Alonso
  • Christopher D. Anderson
  • Krishna G. Aragam
  • Dan E. Arking
  • John Barnard
  • Traci M. Bartz
  • Emelia J. Benjamin
  • Nathan A. Bihlmeyer
  • Joshua C. Bis
  • Heather L. Bloom
  • Eric Boerwinkle
  • Erwin B. Bottinger
  • Jennifer A. Brody
  • Hugh Calkins
  • Archie Campbell
  • Thomas P. Cappola
  • John Carlquist
  • Daniel I. Chasman
  • Lin Y. Chen
  • Yii Der Ida Chen
  • Eue Keun Choi
  • Seung Hoan Choi
  • Ingrid E. Christophersen
  • Mina K. Chung
  • John W. Cole
  • David Conen
  • James Cook
  • Harry J. Crijns
  • Michael J. Cutler
  • Scott M. Damrauer
  • Brian R. Daniels
  • Dawood Darbar
  • Graciela Delgado
  • Joshua C. Denny
  • Martin Dichgans
  • Marcus Dörr
  • Elton A. Dudink
  • Samuel C. Dudley
  • Stefan Gustafsson
  • Cecilia M. Lindgren
  • Steven A Lubitz
  • Kathryn L Lunetta
  • Patrick T Ellinor
Organisations
External organisations
  • Broad Institute
  • Massachusetts General Hospital
  • Copenhagen University Hospital
  • University of Copenhagen
  • Brigham and Women's Hospital / Harvard Medical School
  • Johns Hopkins University School of Medicine
  • Cleveland Clinic Foundation
  • University of Washington
  • Framingham Heart Study
  • Baylor College of Medicine
  • Icahn School of Medicine at Mount Sinai
  • Johns Hopkins University
  • University of Edinburgh
  • University of Pennsylvania
  • Intermountain Medical Center
  • University of Utah
  • University of Minnesota Medical School
  • University of California, Los Angeles
  • Seoul National University Hospital
  • University of Maryland School of Medicine
  • University Hospital Basel
  • Population Health Research Institute, Ontario
  • University of Liverpool
  • Maastricht University Medical Centre
  • University of Illinois at Chicago
  • Heidelberg University
  • Vanderbilt University
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
  • University of Minnesota
  • Uppsala University
  • Wellcome Trust Centre for Human Genetics
  • Skåne University Hospital
  • Boston University
  • National Heart Lung and Blood Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)1225-1233
JournalNature Genetics
Volume50
Issue number9
Early online date2018 Jun 11
Publication statusPublished - 2018 Sep
Publication categoryResearch
Peer-reviewedYes