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

• Published in: Nature genetics Vol. 49; no. 6; pp. 946 - 952
• Main Authors: Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Lin, Honghuang, Arking, Dan E, Smith, Albert V, Albert, Christine M, Chaffin, Mark, Tucker, Nathan R, Li, Molong, Klarin, Derek, Low, Siew-Kee, Müller-Nurasyid, Martina, Dörr, Marcus, Trompet, Stella, Gustafsson, Stefan, Kleber, Marcus E, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Malik, Rainer, Perez, Marco, Sinisalo, Juha, Thériault, Sébastien, Radmanesh, Farid, Teumer, Alexander, Weng, Lu-Chen, Deo, Rajat, Rader, Daniel J, Shah, Svati H, Yang, Qiong, Worrall, Bradford B, Kamatani, Yoichiro, Hagemeijer, Yanick P, Siland, Joylene E, Kubo, Michiaki, Smith, Jonathan D, Bis, Joshua C, Perz, Siegfried, Psaty, Bruce M, Ridker, Paul M, Magnani, Jared W, Harris, Tamara B, Launer, Lenore J, Shoemaker, M Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Kähönen, Mika, Risch, Lorenz, Mansur, Alfredo J, Smith, Blair H, Lu, Yingchang, Bottinger, Erwin B, Hernesniemi, Jussi, Lindgren, Cecilia M, Huang, Jie, Ford, Ian, Delgado, Graciela, Chen, Lin Y, Chen, Yii-Der Ida, Li, Man, Lannfelt, Lars, Rost, Natalia, Taylor, Kent D, Campbell, Archie, Porteous, David, Hocking, Lynne J, Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Denny, Joshua C, Kriebel, Jennifer, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W, Heilmann-Heimbach, Stefanie, Huang, Paul L, Sotoodehnia, Nona, Soliman, Elsayed Z, Uitterlinden, Andre G, Hofman, Albert, Franco, Oscar H, Völker, Uwe, Lin, Henry J, Ingelsson, Erik, Kooperberg, Charles, Conen, David, Rosand, Jonathan, van der Harst, Pim, Kathiresan, Sekar, Stricker, Bruno H, Chung, Mina K, Felix, Stephan B, Gudnason, Vilmundur, Alonso, Alvaro, Kääb, Stefan, Chasman, Daniel I, Benjamin, Emelia J, Tanaka, Toshihiro, Lunetta, Kathryn L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2017; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 631/208/457; 692/308/2056; 692/699/75/29/1309; Agriculture; Analysis; Animal Genetics and Genomics; Atrial fibrillation; Atrial Fibrillation - genetics; Biomedicine; Black or African American - genetics; Cancer Research; Cardiac arrhythmia; Cardiology; Death; Drug discovery; Electrocardiography; Epidemiology; Fibrillation; Forecasts and trends; Gene Function; Gene loci; Genealogy; Genes; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic research; Genetic variation; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Health risks; Heart; Heart diseases; Heart failure; Hospitals; Human Genetics; Humans; Identification and classification; Internal medicine; Laboratories; letter; Medicine; Meta-analysis; Pharmaceutical research; Public health; Quantitative Trait Loci; Risk; Risk factors; Stroke; Studies; Target recognition; Thoracic surgery; White People - genetics; United States > US; California
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3843

Patrick Ellinor and colleagues report meta-analyses of common and rare variant association studies for atrial fibrillation across multiple populations. They identify 12 new loci, some of which implicate genes in atrial electrical and mechanical function. Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death 1 , 2 . Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups 3 , 4 , 5 , 6 , 7 . 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 8 .