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

TitleLarge-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.
Publication TypeJournal Article
Year of Publication2017
AuthorsChristophersen, IE, Rienstra, M, Roselli, C, Yin, X, Geelhoed, B, Barnard, J, Lin, H, Arking, DE, Smith, AV, Albert, CM, Chaffin, M, Tucker, NR, Li, M, Klarin, D, Bihlmeyer, NA, Low, S-K, Weeke, PE, Müller-Nurasyid, M, J Smith, G, Brody, JA, Niemeijer, MN, Dörr, M, Trompet, S, Huffman, J, Gustafsson, S, Schurmann, C, Kleber, ME, Lyytikäinen, L-P, Seppälä, I, Malik, R, Horimoto, ARVR, Perez, M, Sinisalo, J, Aeschbacher, S, Thériault, S, Yao, J, Radmanesh, F, Weiss, S, Teumer, A, Choi, SHoan, Weng, L-C, Clauss, S, Deo, R, Rader, DJ, Shah, SH, Sun, A, Hopewell, JC, Debette, S, Chauhan, G, Yang, Q, Worrall, BB, Paré, G, Kamatani, Y, Hagemeijer, YP, Verweij, N, Siland, JE, Kubo, M, Smith, JD, Van Wagoner, DR, Bis, JC, Perz, S, Psaty, BM, Ridker, PM, Magnani, JW, Harris, TB, Launer, LJ, M Shoemaker, B, Padmanabhan, S, Haessler, J, Bartz, TM, Waldenberger, M, Lichtner, P, Arendt, M, Krieger, JE, Kähönen, M, Risch, L, Mansur, AJ, Peters, A, Smith, BH, Lind, L, Scott, SA, Lu, Y, Bottinger, EB, Hernesniemi, J, Lindgren, CM, Wong, JA, Huang, J, Eskola, M, Morris, AP, Ford, I, Reiner, AP, Delgado, G, Chen, LY, Chen, Y-DIda, Sandhu, RK, Li, M, Boerwinkle, E, Eisele, L, Lannfelt, L, Rost, N, Anderson, CD, Taylor, KD, Campbell, A, Magnusson, PK, Porteous, D, Hocking, LJ, Vlachopoulou, E, Pedersen, NL, Nikus, K, Orho-Melander, M, Hamsten, A, Heeringa, J, Denny, JC, Kriebel, J, Darbar, D, Newton-Cheh, C, Shaffer, C, Macfarlane, PW, Heilmann-Heimbach, S, Almgren, P, Huang, PL, Sotoodehnia, N, Soliman, EZ, Uitterlinden, AG, Hofman, A, Franco, OH, Völker, U, Jöckel, K-H, Sinner, MF, Lin, HJ, Guo, X, Dichgans, M, Ingelsson, E, Kooperberg, C, Melander, O, Loos, RJF, Laurikka, J, Conen, D, Rosand, J, van der Harst, P, Lokki, M-L, Kathiresan, S, Pereira, A, J Jukema, W, Hayward, C, Rotter, JI, Marz, W, Lehtimäki, T, Stricker, BH, Chung, MK, Felix, SB, Gudnason, V, Alonso, A, Roden, DM, Kääb, S, Chasman, DI, Heckbert, SR, Benjamin, EJ, Tanaka, T, Lunetta, KL, Lubitz, SA, Ellinor, PT
Corporate AuthorsMETASTROKE Consortium of the ISGC, Neurology Working Group of the CHARGE Consortium, AFGen Consortium
JournalNat Genet
Volume49
Issue6
Pagination946-952
Date Published2017 Jun
ISSN1546-1718
Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. 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.

DOI10.1038/ng.3843
Alternate JournalNat. Genet.
PubMed ID28416818
Grant ListR01 HL092217 / HL / NHLBI NIH HHS / United States