Meta-analysis identifies six new susceptibility loci for atrial fibrillation

Patrick T. Ellinor, Kathryn L. Lunetta, Christine M. Albert, Nicole L. Glazer, Marylyn D. Ritchie, Albert V. Smith, Dan E. Arking, Martina Müller-Nurasyid, Bouwe P. Krijthe, Steven A. Lubitz, Joshua C. Bis, Mina K. Chung, Marcus Dörr, Kouichi Ozaki, Jason D. Roberts, J. Gustav Smith, Arne Pfeufer, Moritz F. Sinner, Kurt Lohman, Jingzhong DingNicholas L. Smith, Jonathan D. Smith, Michiel Rienstra, Kenneth M. Rice, David R. Van Wagoner, Jared W. Magnani, Reza Wakili, Sebastian Clauss, Jerome I. Rotter, Gerhard Steinbeck, Lenore J. Launer, Robert W. Davies, Matthew Borkovich, Tamara B. Harris, Honghuang Lin, Uwe Völker, Henry Völzke, David J. Milan, Albert Hofman, Eric Boerwinkle, Lin Y. Chen, Elsayed Z. Soliman, Benjamin F. Voight, Guo Li, Aravinda Chakravarti, Michiaki Kubo, Usha B. Tedrow, Lynda M. Rose, Paul M. Ridker, David Conen, Tatsuhiko Tsunoda, Tetsushi Furukawa, Nona Sotoodehnia, Siyan Xu, Naoyuki Kamatani, Daniel Levy, Yusuke Nakamura, Babar Parvez, Saagar Mahida, Karen L. Furie, Jonathan Rosand, Raafia Muhammad, Bruce M. Psaty, Thomas Meitinger, Siegfried Perz, H. Erich Wichmann, Jacqueline C.M. Witteman, W. H.Linda Kao, Sekar Kathiresan, Dan M. Roden, Andre G. Uitterlinden, Fernando Rivadeneira, Barbara McKnight, Marketa Sjögren, Anne B. Newman, Yongmei Liu, Michael H. Gollob, Olle Melander, Toshihiro Tanaka, Bruno H.Ch Stricker, Stephan B. Felix, Alvaro Alonso, Dawood Darbar, John Barnard, Daniel I. Chasman, Susan R. Heckbert, Emelia J. Benjamin, Vilmundur Gudnason, Stefan Kääb

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Abstract

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10-8). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.

Original languageEnglish (US)
Pages (from-to)670-675
Number of pages6
JournalNature Genetics
Volume44
Issue number6
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Genetics

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    Ellinor, P. T., Lunetta, K. L., Albert, C. M., Glazer, N. L., Ritchie, M. D., Smith, A. V., Arking, D. E., Müller-Nurasyid, M., Krijthe, B. P., Lubitz, S. A., Bis, J. C., Chung, M. K., Dörr, M., Ozaki, K., Roberts, J. D., Smith, J. G., Pfeufer, A., Sinner, M. F., Lohman, K., ... Kääb, S. (2012). Meta-analysis identifies six new susceptibility loci for atrial fibrillation. Nature Genetics, 44(6), 670-675. https://doi.org/10.1038/ng.2261