RT Journal Article SR Electronic T1 Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease JF Journal of the American College of Cardiology FD American College of Cardiology SP 823 OP 836 DO 10.1016/j.jacc.2016.11.056 VO 69 IS 7 A1 Webb, Thomas R. A1 Erdmann, Jeanette A1 Stirrups, Kathleen E. A1 Stitziel, Nathan O. A1 Masca, Nicholas G.D. A1 Jansen, Henning A1 Kanoni, Stavroula A1 Nelson, Christopher P. A1 Ferrario, Paola G. A1 König, Inke R. A1 Eicher, John D. A1 Johnson, Andrew D. A1 Hamby, Stephen E. A1 Betsholtz, Christer A1 Ruusalepp, Arno A1 Franzén, Oscar A1 Schadt, Eric E. A1 Björkegren, Johan L.M. A1 Weeke, Peter E. A1 Auer, Paul L. A1 Schick, Ursula M. A1 Lu, Yingchang A1 Zhang, He A1 Dube, Marie-Pierre A1 Goel, Anuj A1 Farrall, Martin A1 Peloso, Gina M. A1 Won, Hong-Hee A1 Do, Ron A1 van Iperen, Erik A1 Kruppa, Jochen A1 Mahajan, Anubha A1 Scott, Robert A. A1 Willenborg, Christina A1 Braund, Peter S. A1 van Capelleveen, Julian C. A1 Doney, Alex S.F. A1 Donnelly, Louise A. A1 Asselta, Rosanna A1 Merlini, Pier A. A1 Duga, Stefano A1 Marziliano, Nicola A1 Denny, Josh C. A1 Shaffer, Christian A1 El-Mokhtari, Nour Eddine A1 Franke, Andre A1 Heilmann, Stefanie A1 Hengstenberg, Christian A1 Hoffmann, Per A1 Holmen, Oddgeir L. A1 Hveem, Kristian A1 Jansson, Jan-Håkan A1 Jöckel, Karl-Heinz A1 Kessler, Thorsten A1 Kriebel, Jennifer A1 Laugwitz, Karl L. A1 Marouli, Eirini A1 Martinelli, Nicola A1 McCarthy, Mark I. A1 Van Zuydam, Natalie R. A1 Meisinger, Christa A1 Esko, Tõnu A1 Mihailov, Evelin A1 Escher, Stefan A. A1 Alver, Maris A1 Moebus, Susanne A1 Morris, Andrew D. A1 Virtamo, Jarma A1 Nikpay, Majid A1 Olivieri, Oliviero A1 Provost, Sylvie A1 AlQarawi, Alaa A1 Robertson, Neil R. A1 Akinsansya, Karen O. A1 Reilly, Dermot F. A1 Vogt, Thomas F. A1 Yin, Wu A1 Asselbergs, Folkert W. A1 Kooperberg, Charles A1 Jackson, Rebecca D. A1 Stahl, Eli A1 Müller-Nurasyid, Martina A1 Strauch, Konstantin A1 Varga, Tibor V. A1 Waldenberger, Melanie A1 , A1 Zeng, Lingyao A1 Chowdhury, Rajiv A1 Salomaa, Veikko A1 Ford, Ian A1 Jukema, J. Wouter A1 Amouyel, Philippe A1 Kontto, Jukka A1 , A1 Nordestgaard, Børge G. A1 Ferrières, Jean A1 Saleheen, Danish A1 Sattar, Naveed A1 Surendran, Praveen A1 Wagner, Aline A1 Young, Robin A1 Howson, Joanna M.M. A1 Butterworth, Adam S. A1 Danesh, John A1 Ardissino, Diego A1 Bottinger, Erwin P. A1 Erbel, Raimund A1 Franks, Paul W. A1 Girelli, Domenico A1 Hall, Alistair S. A1 Hovingh, G. Kees A1 Kastrati, Adnan A1 Lieb, Wolfgang A1 Meitinger, Thomas A1 Kraus, William E. A1 Shah, Svati H. A1 McPherson, Ruth A1 Orho-Melander, Marju A1 Melander, Olle A1 Metspalu, Andres A1 Palmer, Colin N.A. A1 Peters, Annette A1 Rader, Daniel J. A1 Reilly, Muredach P. A1 Loos, Ruth J.F. A1 Reiner, Alex P. A1 Roden, Dan M. A1 Tardif, Jean-Claude A1 Thompson, John R. A1 Wareham, Nicholas J. A1 Watkins, Hugh A1 Willer, Cristen J. A1 Samani, Nilesh J. A1 Schunkert, Heribert A1 Deloukas, Panos A1 Kathiresan, Sekar A1 , YR 2017 UL http://www.onlinejacc.org/content/69/7/823.abstract AB Background Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.Objectives This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.Methods In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.Results We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10−4 with a range of other diseases/traits.Conclusions We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.