Multi-ethnic genome-wide association study for atrial fibrillation.

Published online

Journal Article

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. 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.

Full Text

Duke Authors

Cited Authors

  • Roselli, C; Chaffin, MD; Weng, L-C; Aeschbacher, S; Ahlberg, G; Albert, CM; Almgren, P; Alonso, A; Anderson, CD; Aragam, KG; Arking, DE; Barnard, J; Bartz, TM; Benjamin, EJ; Bihlmeyer, NA; Bis, JC; Bloom, HL; Boerwinkle, E; Bottinger, EB; Brody, JA; Calkins, H; Campbell, A; Cappola, TP; Carlquist, J; Chasman, DI; Chen, LY; Chen, Y-DI; Choi, E-K; Choi, SH; Christophersen, IE; Chung, MK; Cole, JW; Conen, D; Cook, J; Crijns, HJ; Cutler, MJ; Damrauer, SM; Daniels, BR; Darbar, D; Delgado, G; Denny, JC; Dichgans, M; Dörr, M; Dudink, EA; Dudley, SC; Esa, N; Esko, T; Eskola, M; Fatkin, D; Felix, SB; Ford, I; Franco, OH; Geelhoed, B; Grewal, RP; Gudnason, V; Guo, X; Gupta, N; Gustafsson, S; Gutmann, R; Hamsten, A; Harris, TB; Hayward, C; Heckbert, SR; Hernesniemi, J; Hocking, LJ; Hofman, A; Horimoto, ARVR; Huang, J; Huang, PL; Huffman, J; Ingelsson, E; Ipek, EG; Ito, K; Jimenez-Conde, J; Johnson, R; Jukema, JW; Kääb, S; Kähönen, M; Kamatani, Y; Kane, JP; Kastrati, A; Kathiresan, S; Katschnig-Winter, P; Kavousi, M; Kessler, T; Kietselaer, BL; Kirchhof, P; Kleber, ME; Knight, S; Krieger, JE; Kubo, M; Launer, LJ; Laurikka, J; Lehtimäki, T; Leineweber, K; Lemaitre, RN; Li, M; Lim, HE; Lin, HJ; Lin, H; Lind, L; Lindgren, CM; Lokki, M-L; London, B; Loos, RJF; Low, S-K; Lu, Y; Lyytikäinen, L-P; Macfarlane, PW; Magnusson, PK; Mahajan, A; Malik, R; Mansur, AJ; Marcus, GM; Margolin, L; Margulies, KB; März, W; McManus, DD; Melander, O; Mohanty, S; Montgomery, JA; Morley, MP; Morris, AP; Müller-Nurasyid, M; Natale, A; Nazarian, S; Neumann, B; Newton-Cheh, C; Niemeijer, MN; Nikus, K; Nilsson, P; Noordam, R; Oellers, H; Olesen, MS; Orho-Melander, M; Padmanabhan, S; Pak, H-N; Paré, G; Pedersen, NL; Pera, J; Pereira, A; Porteous, D; Psaty, BM; Pulit, SL; Pullinger, CR; Rader, DJ; Refsgaard, L; Ribasés, M; Ridker, PM; Rienstra, M; Risch, L; Roden, DM; Rosand, J; Rosenberg, MA; Rost, N; Rotter, JI; Saba, S; Sandhu, RK; Schnabel, RB; Schramm, K; Schunkert, H; Schurman, C; Scott, SA; Seppälä, I; Shaffer, C; Shah, S; Shalaby, AA; Shim, J; Shoemaker, MB; Siland, JE; Sinisalo, J; Sinner, MF; Slowik, A; Smith, AV; Smith, BH; Smith, JG; Smith, JD; Smith, NL; Soliman, EZ; Sotoodehnia, N; Stricker, BH; Sun, A; Sun, H; Svendsen, JH; Tanaka, T; Tanriverdi, K; Taylor, KD; Teder-Laving, M; Teumer, A; Thériault, S; Trompet, S; Tucker, NR; Tveit, A; Uitterlinden, AG; Van Der Harst, P; Van Gelder, IC; Van Wagoner, DR; Verweij, N; Vlachopoulou, E; Völker, U; Wang, B; Weeke, PE; Weijs, B; Weiss, R; Weiss, S; Wells, QS; Wiggins, KL; Wong, JA; Woo, D; Worrall, BB; Yang, P-S; Yao, J; Yoneda, ZT; Zeller, T; Zeng, L; Lubitz, SA; Lunetta, KL; Ellinor, PT

Published Date

  • June 11, 2018

Published In

Volume / Issue

  • 50 / 9

Start / End Page

  • 1225 - 1233

PubMed ID

  • 29892015

Pubmed Central ID

  • 29892015

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/s41588-018-0133-9

Language

  • eng

Conference Location

  • United States