@Article{Webb_etal2017,
author="Webb, T. R.
and Erdmann, J.
and Stirrups, K. E.
and Stitziel, N. O.
and Masca, N. G. D.
and Jansen, H.
and Kanoni, S.
and Nelson, C. P.
and Ferrario, P. G.
and Konig, I. R.
and Eicher, J. D.
and Johnson, A. D.
and Hamby, S. E.
and Betsholtz, C.
and Ruusalepp, A.
and Franzen, O.
and Schadt, E. E.
and Bjorkegren, J. L. M.
and Weeke, P. E.
and Auer, P. L.
and Schick, U. M.
and Lu, Y.
and Zhang, H.
and Dube, M-P
and Goel, A.
and Farrall, M.
and Peloso, G. M.
and Won, H-H
and Do, R.
and van Iperen, E.
and Kruppa, J.
and Mahajan, A.
and Scott, R. A.
and Willenborg, C.
and Braund, P. S.
and van Capelleveen, J. C.
and Doney, A. S. F.
and Donnelly, L. A.
and Asselta, R.
and Merlini, P. A.
and Duga, S.
and Marziliano, N.
and Denny, J. C.
and Shaffer, C.
and El-Mokhtari, N. E.
and Franke, A.
and Heilmann, S.
and Hengstenberg, C.
and Hoffmann, P.
and Holmen, O. L.
and Hveem, K.
and Jansson, J-H
and Jockel, K-H
and Kessler, T.
and Kriebel, J.
and Laugwitz, K. L.
and Marouli, E.
and Martinelli, N.
and McCarthy, M. I.
and Van Zuydam, N. R.
and Meisinger, C.
and Esko, T.
and Mihailov, E.
and Escher, S. A.
and Alver, M.
and Moebus, S.
and Morris, A. D.
and Virtamo, J.
and Nikpay, M.
and Olivieri, O.
and Provost, S.
and AlQarawi, A.
and Robertson, N. R.
and Akinsansya, K. O.
and Reilly, D. F.
and Vogt, T. F.
and Yin, W.
and Asselbergs, F. W.
and Kooperberg, C.
and Jackson, R. D.
and Stahl, E.
and Muller-Nurasyid, M.
and Strauch, K.
and Varga, T. V.
and Waldenberger, M.
and Zeng, L.
and Chowdhury, R.
and Salomaa, V.
and Ford, I.
and Jukema, J. W.
and Amouyel, P.
and Kontto, J.
and Nordestgaard, B. G.
and Ferrieres, J.
and Saleheen, D.
and Sattar, N.
and Surendran, P.
and Wagner, A.
and Young, R.
and Howson, J. M. M.
and Butterworth, A. S.
and Danesh, J.
and Ardissino, D.
and Bottinger, E. P.
and Erbel, R.
and Franks, P. W.
and Girelli, D.
and Hall, A. S.
and Hovingh, G. K.
and Kastrati, A.
and Lieb, W.
and Meitinger, T.
and Kraus, W. E.
and Shah, S. H.
and McPherson, R.
and Orho-Melander, M.
and Melander, O.
and Metspalu, A.
and Palmer, C. N. A.
and Peters, A.
and Rader, D. J.
and Reilly, M. P.
and Loos, R. J. F.
and Reiner, A. P.
and Roden, D. M.
and Tardif, J-C
and Thompson, J. R.
and Wareham, N. J.
and Watkins, H.
and Willer, C. J.
and Samani, N. J.
and Schunkert, H.
and Deloukas, P.
and Kathiresan, S.",
title="Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease",
journal="Journal of the American College of Cardiology",
year="2017",
volume="69",
number="7",
pages="823--836",
optkeywords="Case-Control Studies; Coronary Artery Disease/epidemiology/*genetics; Female; Gene Frequency; *Genetic Loci; *Genetic Pleiotropy; Genome-Wide Association Study; Humans; Male; Odds Ratio; Polymorphism; Single Nucleotide; cholesteryl ester transfer protein; expression quantitative trait loci; genetics; genome-wide association; single nucleotide polymorphism",
abstract="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 x 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.",
optnote="PMID:28209224; PMCID:PMC5314135",
optnote="exported from refbase (http://vev.medisin.ntnu.no/refbase/show.php?record=2030), last updated on Fri, 02 Feb 2018 16:18:58 +0100",
issn="0735-1097",
doi="10.1016/j.jacc.2016.11.056",
opturl="http://www.ncbi.nlm.nih.gov/pubmed/28209224",
opturl="https://doi.org/10.1016/j.jacc.2016.11.056",
language="English"
}