Large-scale association analysis identifies new risk loci for coronary artery disease.

Published

Journal Article

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

Full Text

Duke Authors

Cited Authors

  • CARDIoGRAMplusC4D Consortium, ; Deloukas, P; Kanoni, S; Willenborg, C; Farrall, M; Assimes, TL; Thompson, JR; Ingelsson, E; Saleheen, D; Erdmann, J; Goldstein, BA; Stirrups, K; König, IR; Cazier, J-B; Johansson, A; Hall, AS; Lee, J-Y; Willer, CJ; Chambers, JC; Esko, T; Folkersen, L; Goel, A; Grundberg, E; Havulinna, AS; Ho, WK; Hopewell, JC; Eriksson, N; Kleber, ME; Kristiansson, K; Lundmark, P; Lyytikäinen, L-P; Rafelt, S; Shungin, D; Strawbridge, RJ; Thorleifsson, G; Tikkanen, E; Van Zuydam, N; Voight, BF; Waite, LL; Zhang, W; Ziegler, A; Absher, D; Altshuler, D; Balmforth, AJ; Barroso, I; Braund, PS; Burgdorf, C; Claudi-Boehm, S; Cox, D; Dimitriou, M; Do, R; DIAGRAM Consortium, ; CARDIOGENICS Consortium, ; Doney, ASF; El Mokhtari, N; Eriksson, P; Fischer, K; Fontanillas, P; Franco-Cereceda, A; Gigante, B; Groop, L; Gustafsson, S; Hager, J; Hallmans, G; Han, B-G; Hunt, SE; Kang, HM; Illig, T; Kessler, T; Knowles, JW; Kolovou, G; Kuusisto, J; Langenberg, C; Langford, C; Leander, K; Lokki, M-L; Lundmark, A; McCarthy, MI; Meisinger, C; Melander, O; Mihailov, E; Maouche, S; Morris, AD; Müller-Nurasyid, M; MuTHER Consortium, ; Nikus, K; Peden, JF; Rayner, NW; Rasheed, A; Rosinger, S; Rubin, D; Rumpf, MP; Schäfer, A; Sivananthan, M; Song, C; Stewart, AFR; Tan, S-T; Thorgeirsson, G; van der Schoot, CE; Wagner, PJ; Wellcome Trust Case Control Consortium, ; Wells, GA; Wild, PS; Yang, T-P; Amouyel, P; Arveiler, D; Basart, H; Boehnke, M; Boerwinkle, E; Brambilla, P; Cambien, F; Cupples, AL; de Faire, U; Dehghan, A; Diemert, P; Epstein, SE; Evans, A; Ferrario, MM; Ferrières, J; Gauguier, D; Go, AS; Goodall, AH; Gudnason, V; Hazen, SL; Holm, H; Iribarren, C; Jang, Y; Kähönen, M; Kee, F; Kim, H-S; Klopp, N; Koenig, W; Kratzer, W; Kuulasmaa, K; Laakso, M; Laaksonen, R; Lee, J-Y; Lind, L; Ouwehand, WH; Parish, S; Park, JE; Pedersen, NL; Peters, A; Quertermous, T; Rader, DJ; Salomaa, V; Schadt, E; Shah, SH; Sinisalo, J; Stark, K; Stefansson, K; Trégouët, D-A; Virtamo, J; Wallentin, L; Wareham, N; Zimmermann, ME; Nieminen, MS; Hengstenberg, C; Sandhu, MS; Pastinen, T; Syvänen, A-C; Hovingh, GK; Dedoussis, G; Franks, PW; Lehtimäki, T; Metspalu, A; Zalloua, PA; Siegbahn, A; Schreiber, S; Ripatti, S; Blankenberg, SS; Perola, M; Clarke, R; Boehm, BO; O'Donnell, C; Reilly, MP; März, W; Collins, R; Kathiresan, S; Hamsten, A; Kooner, JS; Thorsteinsdottir, U; Danesh, J; Palmer, CNA; Roberts, R; Watkins, H; Schunkert, H; Samani, NJ

Published Date

  • January 2013

Published In

Volume / Issue

  • 45 / 1

Start / End Page

  • 25 - 33

PubMed ID

  • 23202125

Pubmed Central ID

  • 23202125

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.2480

Language

  • eng