Meta-analysis identifies six new susceptibility loci for atrial fibrillation

• Published in: Nature genetics Vol. 44; no. 6; pp. 670 - 675
• Main Authors: Ellinor, Patrick T, Lunetta, Kathryn L, Albert, Christine M, Glazer, Nicole L, Ritchie, Marylyn D, Smith, Albert V, Arking, Dan E, Müller-Nurasyid, Martina, Krijthe, Bouwe P, Lubitz, Steven A, Bis, Joshua C, Chung, Mina K, Dörr, Marcus, Ozaki, Kouichi, Roberts, Jason D, Smith, J Gustav, Pfeufer, Arne, Sinner, Moritz F, Lohman, Kurt, Ding, Jingzhong, Smith, Nicholas L, Smith, Jonathan D, Rienstra, Michiel, Rice, Kenneth M, Van Wagoner, David R, Magnani, Jared W, Wakili, Reza, Clauss, Sebastian, Rotter, Jerome I, Steinbeck, Gerhard, Launer, Lenore J, Davies, Robert W, Borkovich, Matthew, Harris, Tamara B, Lin, Honghuang, Völker, Uwe, Völzke, Henry, Milan, David J, Hofman, Albert, Boerwinkle, Eric, Chen, Lin Y, Soliman, Elsayed Z, Voight, Benjamin F, Li, Guo, Chakravarti, Aravinda, Kubo, Michiaki, Tedrow, Usha B, Rose, Lynda M, Ridker, Paul M, Conen, David, Tsunoda, Tatsuhiko, Furukawa, Tetsushi, Sotoodehnia, Nona, Xu, Siyan, Kamatani, Naoyuki, Levy, Daniel, Nakamura, Yusuke, Parvez, Babar, Mahida, Saagar, Furie, Karen L, Rosand, Jonathan, Muhammad, Raafia, Psaty, Bruce M, Meitinger, Thomas, Perz, Siegfried, Wichmann, H-Erich, Witteman, Jacqueline C M, Kao, W H Linda, Kathiresan, Sekar, Roden, Dan M, Uitterlinden, Andre G, Rivadeneira, Fernando, McKnight, Barbara, Sjögren, Marketa, Newman, Anne B, Liu, Yongmei, Gollob, Michael H, Melander, Olle, Tanaka, Toshihiro, Stricker, Bruno H Ch, Felix, Stephan B, Alonso, Alvaro, Darbar, Dawood, Barnard, John, Chasman, Daniel I, Heckbert, Susan R, Benjamin, Emelia J, Gudnason, Vilmundur, Kääb, Stefan
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2012; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/2489/144; 631/443/592/75; Adolescent; Adult; Aged; Aged, 80 and over; Agriculture; Animal Genetics and Genomics; Asian People - genetics; Atrial fibrillation; Atrial Fibrillation - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiac and Cardiovascular Systems; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiology and Cardiovascular Disease; Cardiology. Vascular system; Child; Child, Preschool; Chromosomes; Clinical Medicine; Disease susceptibility; Female; Fundamental and applied biological sciences. Psychology; Gene Function; Gene loci; Gene mutations; Genealogy; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease - genetics; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Health aspects; Heart; Human Genetics; Humans; Infant; Infant, Newborn; Kardiologi; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; letter; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Meta-analysis; Methods; Middle Aged; Musculoskeletal system; Mutation; Polymorphism, Single Nucleotide; Risk Factors; Signal transduction; White People - genetics; Young Adult; United States; Japan; Arrhythmia; Heart disease; Atrial fibrillation; Cardiovascular disease; Identification; Locus; Excitability disorder; Metaanalysis
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2261

Patrick Ellinor and colleagues report a meta-analysis of genome-wide association studies for atrial fibrillation in European populations. They identify six newly associated loci, four of which were replicated in a Japanese study. Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death 1 . 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.