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

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, JB; Johansson, Å; Hall, AS; Lee, JY; 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, LP; 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; Doney, AS; El Mokhtari, N; Eriksson, P; Fischer, K; Fontanillas, P; Franco-Cereceda, A; Gigante, B; Groop, L; Gustafsson, S; Hager, J; Hallmans, G; Han, BG; Hunt, SE; Kang, HM; Illig, T; Kessler, T; Knowles, JW; Kolovou, G; Kuusisto, J; Langenberg, C; Langford, C; Leander, K; Lokki, ML; Lundmark, A; McCarthy, MI; Meisinger, C; Melander, O; Mihailov, E; Maouche, S; Morris, AD; Müller-Nurasyid, M; Nikus, K; Peden, JF; Rayner, NW; Rasheed, A; Rosinger, S; Rubin, D; Rumpf, MP; Schafer, A; Sivananthan, M; Song, C; Stewart, AF; Tan, ST; Thorgeirsson, G; van der Schoot, CE; Wagner, PJ; Wells, GA; Wild, PS; Yang, TP; 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; Ferrieres, J; Gauguier, D; Go, AS; Goodall, AH; Gudnason, V; Hazen, SL; Holm, H; Iribarren, C; Jang, Y; Kähönen, M; Kee, F; Kim, HS; Klopp, N; Koenig, W; Kratzer, W; Kuulasmaa, K; Laakso, M; Laaksonen, R; Lee, JY; 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, DA; Virtamo, J; Wallentin, L; Wareham, N; Zimmermann, ME; Nieminen, MS; Hengstenberg, C; Sandhu, MS; Pastinen, T; Syvänen, AC; 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, CN; Roberts, R; Watkins, H; Schunkert, H; Samani, NJ

doi:10.1038/ng.2480

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journal article

Title:: Large-scale association analysis identifies new risk loci for coronary artery disease.
Document type:: Journal Article; Article
Author(s):: 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, JB; Johansson, Å; Hall, AS; Lee, JY; 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, LP; 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; Doney, AS; El Mokhtari, N; Eriksson, P; Fischer, K; Fontanillas, P; Franco-Cereceda, A; Gigante, B; Groop, L; Gustafsson, S; Hager, J; Hallmans, G; Han, BG; Hunt, SE; Kang, HM; Illig, T; Kessler, T; Knowles, JW; Kolovou, G; Kuusisto, J; Langenberg, C; Langford, C; Leander, K; Lokki, ML; Lundmark, A; McCarthy, MI; Meisinger, C; Melander, O; Mihailov, E; Maouche, S; Morris, AD; Müller-Nurasyid, M; Nikus, K; Peden, JF; Rayner, NW; Rasheed, A; Rosinger, S; Rubin, D; Rumpf, MP; Schafer, A; Sivananthan, M; Song, C; Stewart, AF; Tan, ST; Thorgeirsson, G; van der Schoot, CE; Wagner, PJ; Wells, GA; Wild, PS; Yang, TP; 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; Ferrieres, J; Gauguier, D; Go, AS; Goodall, AH; Gudnason, V; Hazen, SL; Holm, H; Iribarren, C; Jang, Y; Kähönen, M; Kee, F; Kim, HS; Klopp, N; Koenig, W; Kratzer, W; Kuulasmaa, K; Laakso, M; Laaksonen, R; Lee, JY; 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, DA; Virtamo, J; Wallentin, L; Wareham, N; Zimmermann, ME; Nieminen, MS; Hengstenberg, C; Sandhu, MS; Pastinen, T; Syvänen, AC; 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, CN; Roberts, R; Watkins, H; Schunkert, H; Samani, NJ «
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, JB; Johansson, Å; Hall, AS; Lee, JY; 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, LP; Rafelt, S; Shungin, D; Strawbridge, RJ; Thorleifsson, G; Tikkanen, E; Van Zuydam, N; Voight, BF; Waite, LL; Zhang, W;... »
Abstract:: 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.
Journal title abbreviation:: Nat Genet
Year:: 2013
Journal volume:: 45
Journal issue:: 1
Pages contribution:: 25-33
Language:: eng
Fulltext / DOI:: doi:10.1038/ng.2480
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/23202125
Print-ISSN:: 1061-4036
TUM Institution:: Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Lehr- und Forschungskooperationen mit den Kliniken und Instituten am Deutschen Herzzentrum Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (DHM) (Prof. Schunkert)2013

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