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Author (up) Webb, T.R.; Erdmann, J.; Stirrups, K.E.; Stitziel, N.O.; Masca, N.G.D.; Jansen, H.; Kanoni, S.; Nelson, C.P.; Ferrario, P.G.; Konig, I.R.; Eicher, J.D.; Johnson, A.D.; Hamby, S.E.; Betsholtz, C.; Ruusalepp, A.; Franzen, O.; Schadt, E.E.; Bjorkegren, J.L.M.; Weeke, P.E.; Auer, P.L.; Schick, U.M.; Lu, Y.; Zhang, H.; Dube, M.-P.; Goel, A.; Farrall, M.; Peloso, G.M.; Won, H.-H.; Do, R.; van Iperen, E.; Kruppa, J.; Mahajan, A.; Scott, R.A.; Willenborg, C.; Braund, P.S.; van Capelleveen, J.C.; Doney, A.S.F.; Donnelly, L.A.; Asselta, R.; Merlini, P.A.; Duga, S.; Marziliano, N.; Denny, J.C.; Shaffer, C.; El-Mokhtari, N.E.; Franke, A.; Heilmann, S.; Hengstenberg, C.; Hoffmann, P.; Holmen, O.L.; Hveem, K.; Jansson, J.-H.; Jockel, K.-H.; Kessler, T.; Kriebel, J.; Laugwitz, K.L.; Marouli, E.; Martinelli, N.; McCarthy, M.I.; Van Zuydam, N.R.; Meisinger, C.; Esko, T.; Mihailov, E.; Escher, S.A.; Alver, M.; Moebus, S.; Morris, A.D.; Virtamo, J.; Nikpay, M.; Olivieri, O.; Provost, S.; AlQarawi, A.; Robertson, N.R.; Akinsansya, K.O.; Reilly, D.F.; Vogt, T.F.; Yin, W.; Asselbergs, F.W.; Kooperberg, C.; Jackson, R.D.; Stahl, E.; Muller-Nurasyid, M.; Strauch, K.; Varga, T.V.; Waldenberger, M.; Zeng, L.; Chowdhury, R.; Salomaa, V.; Ford, I.; Jukema, J.W.; Amouyel, P.; Kontto, J.; Nordestgaard, B.G.; Ferrieres, J.; Saleheen, D.; Sattar, N.; Surendran, P.; Wagner, A.; Young, R.; Howson, J.M.M.; Butterworth, A.S.; Danesh, J.; Ardissino, D.; Bottinger, E.P.; Erbel, R.; Franks, P.W.; Girelli, D.; Hall, A.S.; Hovingh, G.K.; Kastrati, A.; Lieb, W.; Meitinger, T.; Kraus, W.E.; Shah, S.H.; McPherson, R.; Orho-Melander, M.; Melander, O.; Metspalu, A.; Palmer, C.N.A.; Peters, A.; Rader, D.J.; Reilly, M.P.; Loos, R.J.F.; Reiner, A.P.; Roden, D.M.; Tardif, J.-C.; Thompson, J.R.; Wareham, N.J.; Watkins, H.; Willer, C.J.; Samani, N.J.; Schunkert, H.; Deloukas, P.; Kathiresan, S. url  doi
  Title Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease Type Journal Article
  Year 2017 Publication Journal of the American College of Cardiology Abbreviated Journal J Am Coll Cardiol  
  Volume 69 Issue 7 Pages 823-836  
  Keywords 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.  
  Address Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts  
  Corporate Author Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia Investigators Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0735-1097 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28209224; PMCID:PMC5314135 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2030  
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