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.