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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Webb, Thomas R. (author)
Erdmann, Jeanette (author)
Stirrups, Kathleen E. (author)
show more...
Stitziel, Nathan O. (author)
Masca, Nicholas G. D. (author)
Jansen, Henning (author)
Kanoni, Stavroula (author)
Nelson, Christopher P. (author)
Ferrario, Paola G. (author)
Koenig, Inke R. (author)
Eicher, John D. (author)
Johnson, Andrew D. (author)
Hamby, Stephen E. (author)
Betsholtz, Christer (author)
Ruusalepp, Arno (author)
Franzen, Oscar (author)
Schadt, Eric E. (author)
Bjoerkegren, Johan L. M. (author)
Weeke, Peter E. (author)
Auer, Paul L. (author)
Schick, Ursula M. (author)
Lu, Yingchang (author)
Zhang, He (author)
Dube, Marie-Pierre (author)
Goel, Anuj (author)
Farrall, Martin (author)
Peloso, Gina M. (author)
Won, Hong-Hee (author)
Do, Ron (author)
van Iperen, Erik (author)
Kruppa, Jochen (author)
Mahajan, Anubha (author)
Scott, Robert A. (author)
Willenborg, Christina (author)
Braund, Peter S. (author)
van Capelleveen, Julian C. (author)
Doney, Alex S. F. (author)
Donnelly, Louise A. (author)
Asselta, Rosanna (author)
Merlini, Pier A. (author)
Duga, Stefano (author)
Marziliano, Nicola (author)
Denny, Josh C. (author)
Shaffer, Christian (author)
El-Mokhtari, Nour Eddine (author)
Franke, Andre (author)
Heilmann, Stefanie (author)
Hengstenberg, Christian (author)
Hoffmann, Per (author)
Holmen, Oddgeir L. (author)
Hveem, Kristian (author)
Jansson, Jan-Hakan (author)
Joeckel, Karl-Heinz (author)
Kessler, Thorsten (author)
Kriebel, Jennifer (author)
Laugwitz, Karl L. (author)
Marouli, Eirini (author)
Martinelli, Nicola (author)
McCarthy, Mark I. (author)
Van Zuydam, Natalie R. (author)
Meisinger, Christa (author)
Esko, Tonu (author)
Mihailov, Evelin (author)
Escher, Stefan A. (author)
Alver, Maris (author)
Moebus, Susanne (author)
Morris, Andrew D. (author)
Virtamo, Jarma (author)
Nikpay, Majid (author)
Olivieri, Oliviero (author)
Provost, Sylvie (author)
AlQarawi, Alaa (author)
Robertson, Neil R. (author)
Akinsansya, Karen O. (author)
Reilly, Dermot F. (author)
Vogt, Thomas F. (author)
Yin, Wu (author)
Asselbergs, Folkert W. (author)
Kooperberg, Charles (author)
Jackson, Rebecca D. (author)
Stahl, Eli (author)
Mueller-Nurasyid, Martina (author)
Strauch, Konstantin (author)
Varga, Tibor V. (author)
Waldenberger, Melanie (author)
Zeng, Lingyao (author)
Chowdhury, Rajiv (author)
Salomaa, Veikko (author)
Ford, Ian (author)
Jukema, J. Wouter (author)
Amouyel, Philippe (author)
Kontto, Jukka (author)
Nordestgaard, Borge G. (author)
Ferrieres, Jean (author)
Saleheen, Danish (author)
Sattar, Naveed (author)
Surendran, Praveen (author)
Wagner, Aline (author)
Young, Robin (author)
Howson, Joanna M. M. (author)
Butterworth, Adam S. (author)
Danesh, John (author)
Ardissino, Diego (author)
Bottinger, Erwin P. (author)
Erbel, Raimund (author)
Franks, Paul W. (author)
Girelli, Domenico (author)
Hall, Alistair S. (author)
Hovingh, G. Kees (author)
Kastrati, Adnan (author)
Lieb, Wolfgang (author)
Meitinger, Thomas (author)
Kraus, William E. (author)
Shah, Svati H. (author)
McPherson, Ruth (author)
Orho-Melander, Marju (author)
Melander, Olle (author)
Metspalu, Andres (author)
Palmer, Colin N. A. (author)
Peters, Annette (author)
Rader, Daniel J. (author)
Reilly, Muredach P. (author)
Loos, Ruth J. F. (author)
Reiner, Alex P. (author)
Roden, Dan M. (author)
Tardif, Jean-Claude (author)
Thompson, John R. (author)
Wareham, Nicholas J. (author)
Watkins, Hugh (author)
Willer, Cristen J. (author)
Samani, Nilesh J. (author)
Schunkert, Heribert (author)
Deloukas, Panos (author)
Kathiresan, Sekar (author)
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 (publisher)
2017
2017
English.
In: Journal of the American College of Cardiology. - 0735-1097. ; 69:7, 823-836
  • swepub:Mat__t
Abstract Subject headings
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  • 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.

Subject headings

Medical and Health Sciences  (hsv)
Medicin och hälsovetenskap  (hsv)

Keyword

cholesteryl ester transfer protein
expression quantitative trait loci
genetics
genome-wide association
single nucleotide polymorphism

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By the author/editor
Webb, Thomas R.
Erdmann, Jeanett ...
Stirrups, Kathle ...
Stitziel, Nathan ...
Masca, Nicholas ...
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Betsholtz, Chris ...
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Schadt, Eric E.
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Weeke, Peter E.
Auer, Paul L.
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Zhang, He
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Franke, Andre
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Holmen, Oddgeir ...
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Kessler, Thorste ...
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Laugwitz, Karl L ...
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Martinelli, Nico ...
McCarthy, Mark I ...
Van Zuydam, Nata ...
Meisinger, Chris ...
Esko, Tonu
Mihailov, Evelin
Escher, Stefan A ...
Alver, Maris
Moebus, Susanne
Morris, Andrew D ...
Virtamo, Jarma
Nikpay, Majid
Olivieri, Olivie ...
Provost, Sylvie
AlQarawi, Alaa
Robertson, Neil ...
Akinsansya, Kare ...
Reilly, Dermot F ...
Vogt, Thomas F.
Yin, Wu
Asselbergs, Folk ...
Kooperberg, Char ...
Jackson, Rebecca ...
Stahl, Eli
Mueller-Nurasyid ...
Strauch, Konstan ...
Varga, Tibor V.
Waldenberger, Me ...
Zeng, Lingyao
Chowdhury, Rajiv
Salomaa, Veikko
Ford, Ian
Jukema, J. Woute ...
Amouyel, Philipp ...
Kontto, Jukka
Nordestgaard, Bo ...
Ferrieres, Jean
Saleheen, Danish
Sattar, Naveed
Surendran, Prave ...
Wagner, Aline
Young, Robin
Howson, Joanna M ...
Butterworth, Ada ...
Danesh, John
Ardissino, Diego
Bottinger, Erwin ...
Erbel, Raimund
Franks, Paul W.
Girelli, Domenic ...
Hall, Alistair S ...
Hovingh, G. Kees
Kastrati, Adnan
Lieb, Wolfgang
Meitinger, Thoma ...
Kraus, William E ...
Shah, Svati H.
McPherson, Ruth
Orho-Melander, M ...
Melander, Olle
Metspalu, Andres
Palmer, Colin N. ...
Peters, Annette
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Reilly, Muredach ...
Loos, Ruth J. F.
Reiner, Alex P.
Roden, Dan M.
Tardif, Jean-Cla ...
Thompson, John R ...
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Schunkert, Herib ...
Deloukas, Panos
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