Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

H. Schunkert, I.R. Konig, S. Kathiresan, M.P. Reilly, T.L. Assimes, H. Holm, M. Preuss, A.F.R. Stewart, M. Barbalic, C. Gieger, D. Absher, Z. Aherrahrou, H. Allayee, D. Altshuler, S.S. Anand, K. Andersen, J.L. Anderson, D. Ardissino, S.G. Ball, A.J. BalmforthT.A. Barnes, D.M. Becker, L.C. Becker, K. Berger, J.C. Bis, S.M. Boekholdt, E. Boerwinkle, P.S. Braund, M.J. Brown, M.S. Burnett, I. Buysschaert, J.F. Carlquist, L. Chen, S. Cichon, V. Codd, R.W. Davies, G. Dedoussis, A. Dehghan, S. Demissie, J.M. Devaney, P. Diemert, R. Do, A. Doering, S. Eifert, N.E. El Mokhtari, S.G. Ellis, R. Elosua, J.C. Engert, S.E. Epstein, U. De Faire, M. Fischer, A.R. Folsom, J. Freyer, B. Gigante, D. Girelli, S. Gretarsdottir, V. Gudnason, J.R. Gulcher, E. Halperin, N. Hammond, S.L. Hazen, A. Hofman, B.D. Horne, T. Illig, C. Iribarren, G.T. Jones, J.W. Jukema, M.A. Kaiser, L.M. Kaplan, J.J.P. Kastelein, K.T. Khaw, J.W. Knowles, G. Kolovou, A. Kong, R. Laaksonen, D. Lambrechts, K. Leander, G. Lettre, M.Y. Li, W. Lieb, C. Loley, A.J. Lotery, P.M. Mannucci, S. Maouche, N. Martinelli, Pascal McKeown, C. Meisinger, T. Meitinger, O. Melander, P.A. Merlini, V. Mooser, T. Morgan, T.W. Muhleisen, J.B. Muhlestein, T. Munzel, K. Musunuru, J. Nahrstaedt, C.P. Nelson, M.M. Nothen, O. Olivieri, R.S. Patel, Christopher Patterson, A. Peters, F. Peyvandi, L. Qu, A.A. Quyyumi, D.J. Rader, L.S. Rallidis, C. Rice, F.R. Rosendaal, D. Rubin, V. Salomaa, M.L. Sampietro, M.S. Sandhu, E. Schadt, A. Schafer, A. Schillert, S. Schreiber, J. Schrezenmeir, S.M. Schwartz, D.S. Siscovick, M. Sivananthan, S. Sivapalaratnam, A. Smith, T.B. Smith, J.D. Snoep, N. Soranzo, J.A. Spertus, K. Stark, K. Stirrups, M. Stoll, W.H.W. Tang, S. Tennstedt, G. Thorgeirsson, G. Thorleifsson, M. Tomaszewski, A.G. Uitterlinden, A.M. Van Rij, B.F. Voight, N.J. Wareham, G.A. Wells, H.E. Wichmann, P.S. Wild, C. Willenborg, J.C.M. Witteman, B.J. Wright, S. Ye, T. Zeller, A. Ziegler, F. Cambien, A.H. Goodall, L.A. Cupples, T. Quertermous, W. Marz, C. Hengstenberg, S. Blankenberg, W.H. Ouwehand, A.S. Hall, P. Deloukas, J.R. Thompson, K. Stefansson, R. Roberts, U. Thorsteinsdottir, C.J. O'Donnell, Ruth McPherson, J. Erdmann, N.J. Samani

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Abstract

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
Original languageEnglish
Pages (from-to)333-U153
JournalNature Genetics
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2011

ASJC Scopus subject areas

  • Genetics

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