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Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Research output: Contribution to journalArticle

  • Ingrid E Christophersen
  • Michiel Rienstra
  • Carolina Roselli
  • Xiaoyan Yin
  • Bastiaan Geelhoed
  • John Barnard
  • Honghuang Lin
  • Dan E Arking
  • Albert V Smith
  • Christine M Albert
  • Mark Chaffin
  • Nathan R Tucker
  • Molong Li
  • Derek Klarin
  • Nathan A Bihlmeyer
  • Siew-Kee Low
  • Peter E Weeke
  • Martina Müller-nurasyid
  • J Gustav Smith
  • Jennifer A Brody
  • Maartje N Niemeijer
  • Marcus Dörr
  • Stella Trompet
  • Jennifer Huffman
  • Stefan Gustafsson
  • Claudia Schurmann
  • Marcus E Kleber
  • Leo-Pekka Lyytikäinen
  • Ilkka Seppälä
  • Rainer Malik
  • Andrea R V R Horimoto
  • Marco Perez
  • Juha Sinisalo
  • Stefanie Aeschbacher
  • Sébastien Thériault
  • Jie Yao
  • Farid Radmanesh
  • Stefan Weiss
  • Alexander Teumer
  • Seung Hoan Choi
  • Lu-Chen Weng
  • Sebastian Clauss
  • Rajat Deo
  • Daniel J Rader
  • Svati H Shah
  • Albert Sun
  • Andrew P Morris
  • Archie Campbell
  • David Porteous
  • METASTROKE Consortium of the ISGC
  • The Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
  • Caroline Hayward
  • AFGen Consortium

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Original languageEnglish
Pages (from-to)946-952
Number of pages7
JournalNature Genetics
Volume49
Issue number6
Early online date17 Apr 2017
DOIs
Publication statusPublished - Jun 2017

Abstract

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.

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