Multi-ethnic genome-wide association study for atrial fibrillation

Roselli, Carolina; Chaffin, Mark D.; Weng, Lu-Chen; Aeschbacher, Stefanie; Ahlberg, Gustav; Albert, Christine M.; Almgren, Peter; Alonso, Alvaro; Anderson, Christopher D.; Aragam, Krishna G.; Arking, Dan E.; Barnard, John; Bartz, Traci M.; Benjamin, Emelia J.; Bihlmeyer, Nathan A.; Bis, Joshua C.; Bloom, Heather L.; Börwinkle, Eric; Bottinger, Erwin B.; Brody, Jennifer A.; Calkins, Hugh; Campbell, Archie; Cappola, Thomas P.; Carlquist, John; Chasman, Daniel I.; Chen, Lin Y.; Chen, Yii-Der Ida; Choi, Eue-Keun; Choi, Seung Hoan; Christophersen, Ingrid E.; Chung, Mina K.; Cole, John W.; Conen, David; Cook, James; Crijns, Harry J.; Cutler, Michael J.; Damrauer, Scott M.; Daniels, Brian R.; Darbar, Dawood; Delgado, Graciela; Denny, Joshua C.; Dichgans, Martin ; Dörr, Marcus; Dudink, Elton A.; Dudley, Samuel C.; Esa, Nada; Esko, Tonu; Eskola, Markku; Fatkin, Diane; Felix, Stephan B.; Ford, Ian; Franco, Oscar H.; Geelhoed, Bastiaan; Grewal, Raji P.; Gudnason, Vilmundur; Guo, Xiuqing; Gupta, Namrata; Gustafsson, Stefan; Gutmann, Rebecca; Hamsten, Anders; Harris, Tamara B.; Hayward, Caroline; Heckbert, Susan R.; Hernesniemi, Jussi; Hocking, Lynne J.; Hofman, Albert; Horimoto, Andrea R. V. R.; Huang, Jie; Huang, Paul L.; Huffman, Jennifer; Ingelsson, Erik; Ipek, Esra Gucuk; Ito, Kaoru; Jimenez-Conde, Jordi; Johnson, Renee; Jukema, J. Wouter; Kääb, Stefan; Kahonen, Mika; Kamatani, Yoichiro; Kane, John P.; Kastrati, Adnan; Kathiresan, Sekar; Katschnig-Winter, Petra; Kavousi, Maryam; Kessler, Thorsten; Kietselaer, Bas L.; Kirchhof, Paulus; Kleber, Marcus E.; Knight, Stacey; Krieger, Jose E.; Kubo, Michiaki; Launer, Lenore J.; Laurikka, Jari; Lehtimaki, Terho; Leineweber, Kirsten; Lemaitre, Rozenn N.; Li, Man; Lim, Hong Euy; Lin, Henry J.; Lin, Honghuang; Lind, Lars; Lindgren, Cecilia M.; Lokki, Marja-Liisa; London, Barry; Loos, Ruth J. F.; Low, Siew-Kee; Lu, Yingchang; Lyytikainen, Leo-Pekka; Macfarlane, Peter W.; Magnusson, Patrik K.; Mahajan, Anubha; Malik, Rainer; Mansur, Alfredo J.; Marcus, Gregory M.; Margolin, Lauren; Margulies, Kenneth B.; Maerz, Winfried; McManus, David D.; Melander, Olle; Mohanty, Sanghamitra; Montgomery, Jay A.; Morley, Michael P.; Morris, Andrew P.; Müller-Nurasyid, Martina; Natale, Andrea; Nazarian, Saman; Neumann, Benjamin; Newton-Cheh, Christopher; Niemeijer, Maartje N.; Nikus, Kjell; Nilsson, Peter; Noordam, Raymond; Oellers, Heidi; Olesen, Morten S.; Orho-Melander, Marju; Padmanabhan, Sandosh; Pak, Hui-Nam; Pare, Guillaume; Pedersen, Nancy L.; Pera, Joanna; Pereira, Alexandre; Porteous, David; Psaty, Bruce M.; Pulit, Sara L.; Pullinger, Clive R.; Rader, Daniel J.; Refsgaard, Lena; Ribases, Marta; Ridker, Paul M.; Rienstra, Michiel; Risch, Lorenz; Roden, Dan M.; Rosand, Jonathan; Rosenberg, Michael A.; Rost, Natalia; Rotter, Jerome I.; Saba, Samir; Sandhu, Roopinder K.; Schnabel, Renate B.; Schramm, Katharina; Schunkert, Heribert; Schurman, Claudia; Scott, Stuart A.; Seppala, Ilkka; Shaffer, Christian; Shah, Svati; Shalaby, Alaa A.; Shim, Jaemin; Shoemaker, M. Benjamin; Siland, Joylene E.; Sinisalo, Juha; Sinner, Moritz F.; Slowik, Agnieszka; Smith, Albert V.; Smith, Blair H.; Smith, J. Gustav; Smith, Jonathan D.; Smith, Nicholas L.; Soliman, Elsayed Z.; Sotoodehnia, Nona; Stricker, Bruno H.; Sun, Albert; Sun, Han; Svendsen, Jesper H.; Tanaka, Toshihiro; Tanriverdi, Kahraman; Taylor, Kent D.; Teder-Laving, Maris; Teumer, Alexander; Theriault, Sebastien; Trompet, Stella; Tucker, Nathan R.; Tveit, Arnljot; Uitterlinden, Andre G.; Harst, Pim van der; Gelder, Isabelle C. van; Wagoner, David R. van; Verweij, Niek; Vlachopoulou, Efthymia; Voelker, Uwe; Wang, Biqi; Weeke, Peter E.; Weijs, Bob; Weiss, Raul; Weiss, Stefan; Wells, Quinn S.; Wiggins, Kerri L.; Wong, Jorge A.; Woo, Daniel; Worrall, Bradford B.; Yang, Pil-Sung; Yao, Jie; Yoneda, Zachary T.; Zeller, Tanja; Zeng, Lingyao; Lubitz, Steven A.; Lunetta, Kathryn L. and Ellinor, Patrick T. (2018): Multi-ethnic genome-wide association study for atrial fibrillation. In: Nature Genetics, Vol. 50, No. 9: pp. 1225-1233

Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). 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.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Institute for Stroke and Dementia Research (ISD)
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1061-4036
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198