Multi-ethnic genome-wide association study for atrial fibrillation

Carolina Roselli, Mark D. Chaffin, Lu-Chen Weng, Stefanie Aeschbacher, Gustav Ahlberg, Christine M. Albert, Peter Almgren, Alvaro Alonso, Christopher D. Anderson, Krishna G. Aragam, Dan E. Arking, John Barnard, Traci M. Bartz, Emelia J. Benjamin, Nathan A. Bihlmeyer, Joshua C. Bis, Heather L. Bloom, Eric Boerwinkle, Erwin B. Bottinger, Jennifer A. Brody, Hugh Calkins, Archie Campbell, Thomas P. Cappola, John Carlquist, Daniel I. Chasman, Lin Y. Chen, Yii-Der Ida Chen, Eue-Keun Choi, Seung Hoan Choi, Ingrid E. Christophersen, Mina K. Chung, John W. Cole, David Conen, James Cook, Harry J. Crijns, Michael J. Cutler, Scott M. Damrauer, Brian R. Daniels, Dawood Darbar, Graciela Delgado, Joshua C. Denny, Martin Dichgans, Marcus Dörr, Elton A. Dudink, Samuel C. Dudley, Nada Esa, Tonu Esko, Markku Eskola, Diane Fatkin, Stephan B. Felix, Ian Ford, Oscar H. Franco, Bastiaan Geelhoed, Raji P. Grewal, Vilmundur Gudnason, Xiuqing Guo, Namrata Gupta, Stefan Gustafsson, Rebecca Gutmann, Anders Hamsten, Tamara B. Harris, Caroline Hayward, Susan R. Heckbert, Jussi Hernesniemi, Lynne J. Hocking, Albert Hofman, Andrea R. V. R. Horimoto, Jie Huang, Paul L. Huang, Jennifer Huffman, Erik Ingelsson, Esra Gucuk Ipek, Kaoru Ito, Jordi Jimenez-Conde, Renee Johnson, J. Wouter Jukema, Stefan Kääb, Mika Kähönen, Yoichiro Kamatani, John P. Kane, Adnan Kastrati, Sekar Kathiresan, Petra Katschnig-Winter, Maryam Kavousi, Thorsten Kessler, Bas L. Kietselaer, Paulus Kirchhof, Marcus E. Kleber, Stacey Knight, Jose E. Krieger, Michiaki Kubo, Lenore J. Launer, Jari Laurikka, Terho Lehtimäki, Kirsten Leineweber, Rozenn N. Lemaitre, Man Li, Hong Euy Lim, Henry J. Lin, Honghuang Lin, Lars Lind, Cecilia M. Lindgren, Marja-Liisa Lokki, Barry London, Ruth J. F. Loos, Siew-Kee Low, Yingchang Lu, Leo-Pekka Lyytikäinen, Peter W. Macfarlane, Patrik K. Magnusson, Anubha Mahajan, Rainer Malik, Alfredo J. Mansur, Gregory M. Marcus, Lauren Margolin, Kenneth B. Margulies, Winfried März, David D. McManus, Olle Melander, Sanghamitra Mohanty, Jay A. Montgomery, Michael P. Morley, Andrew P. Morris, Martina Müller-Nurasyid, Andrea Natale, Saman Nazarian, Benjamin Neumann, Christopher Newton-Cheh, Maartje N. Niemeijer, Kjell Nikus, Peter Nilsson, Raymond Noordam, Heidi Oellers, Morten S. Olesen, Marju Orho-Melander, Sandosh Padmanabhan, Hui-Nam Pak, Guillaume Paré, Nancy L. Pedersen, Joanna Pera, Alexandre Pereira, David Porteous, Bruce M. Psaty, Sara L. Pulit, Clive R. Pullinger, Daniel J. Rader, Lena Refsgaard, Marta Ribasés, Paul M. Ridker, Michiel Rienstra, Lorenz Risch, Dan M. Roden, Jonathan Rosand, Michael A. Rosenberg, Natalia Rost, Jerome I. Rotter, Samir Saba, Roopinder K. Sandhu, Renate B. Schnabel, Katharina Schramm, Heribert Schunkert, Claudia Schurman, Stuart A. Scott, Ilkka Seppälä, Christian Shaffer, Svati Shah, Alaa A. Shalaby, Jaemin Shim, M. Benjamin Shoemaker, Joylene E. Siland, Juha Sinisalo, Moritz F. Sinner, Agnieszka Slowik, Albert V. Smith, Blair H. Smith, J. Gustav Smith, Jonathan D. Smith, Nicholas L. Smith, Elsayed Z. Soliman, Nona Sotoodehnia, Bruno H. Stricker, Albert Sun, Han Sun, Jesper H. Svendsen, Toshihiro Tanaka, Kahraman Tanriverdi, Kent D. Taylor, Maris Teder-Laving, Alexander Teumer, Sébastien Thériault, Stella Trompet, Nathan R. Tucker, Arnljot Tveit, Andre G. Uitterlinden, Pim Van Der Harst, Isabelle C. Van Gelder, David R. Van Wagoner, Niek Verweij, Efthymia Vlachopoulou, Uwe Völker, Biqi Wang, Peter E. Weeke, Bob Weijs, Raul Weiss, Stefan Weiss, Quinn S. Wells, Kerri L. Wiggins, Jorge A. Wong, Daniel Woo, Bradford B. Worrall, Pil-Sung Yang, Jie Yao, Zachary T. Yoneda, Tanja Zeller, Lingyao Zeng, Steven A. Lubitz, Kathryn L. Lunetta, Patrick T. Ellinor

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.