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Nature Genetics

Publication date: 2011-04-01
Volume: 43 Pages: 333 - 338
Publisher: Nature Publishing Group

Author:

Schunkert, Heribert
König, Inke R ; Kathiresan, Sekar ; Reilly, Muredach P ; Assimes, Themistocles L ; Holm, Hilma ; Preuss, Michael ; Stewart, Alexandre FR ; Barbalic, Maja ; Gieger, Christian ; Absher, Devin ; Chen, Li ; Cichon, Sven ; Codd, Veryan ; Davies, Robert W ; Dedoussis, George ; Dehghan, Abbas ; Demissie, Serkalem ; Devaney, Joseph M ; Diemert, Patrick ; Doering, Angela ; Patterson, Chris C ; Eifert, Sandra ; Mokhtari, Nour Eddine El ; Ellis, Stephen G ; Elosua, Roberto ; Engert, James C ; Epstein, Stephen E ; de Faire, Ulf ; Fischer, Marcus ; Folsom, Aaron R ; Freyer, Jennifer ; Peters, Annette ; Gigante, Bruna ; Girelli, Domenico ; Gretarsdottir, Solveig ; Gudnason, Vilmundur ; Gulcher, Jeffrey R ; Halperin, Eran ; Hammond, Naomi ; Hazen, Stanley L ; Hofman, Albert ; Horne, Benjamin D ; Peyvandi, Flora ; Illig, Thomas ; Iribarren, Carlos ; Jones, Gregory T ; Jukema, J Wouter ; Kaiser, Michael A ; Kaplan, Lee M ; Kastelein, John JP ; Khaw, Kay-Tee ; Knowles, Joshua W ; Kolovou, Genovefa ; Qu, Liming ; Kong, Augustine ; Laaksonen, Reijo ; Lambrechts, Diether ; Leander, Karin ; Lettre, Guillaume ; Lieb, Wolfgang ; Loley, Christina ; Lotery, Andrew J ; Mannucci, Pier M ; Maouche, Seraya ; Quyyumi, Arshed A ; Martinelli, Nicola ; McKeown, Pascal P ; Meisinger, Christa ; Meitinger, Thomas ; Melander, Olle ; Merlini, Pier Angelica ; Mooser, Vincent ; Morgan, Thomas ; Mühleisen, Thomas W ; Muhlestein, Joseph B ; Rader, Daniel J ; Münzel, Thomas ; Musunuru, Kiran ; Nahrstaedt, Janja ; Nelson, Christopher P ; Nöthen, Markus M ; Olivieri, Oliviero ; Patel, Riyaz S ; Rallidis, Loukianos S ; Rice, Catherine ; Rosendaal, Frits R ; Rubin, Diana ; Aherrahrou, Zouhair ; Salomaa, Veikko ; Sampietro, M Lourdes ; Sandhu, Manj S ; Schadt, Eric ; Schäfer, Arne ; Schillert, Arne ; Schreiber, Stefan ; Schrezenmeir, Jürgen ; Schwartz, Stephen M ; Siscovick, David S ; Allayee, Hooman ; Sivananthan, Mohan ; Sivapalaratnam, Suthesh ; Smith, Albert ; Smith, Tamara B ; Snoep, Jaapjan D ; Soranzo, Nicole ; Spertus, John A ; Stark, Klaus ; Stirrups, Kathy ; Stoll, Monika ; Altshuler, David ; Tang, WH Wilson ; Tennstedt, Stephanie ; Thorgeirsson, Gudmundur ; Thorleifsson, Gudmar ; Tomaszewski, Maciej ; Uitterlinden, Andre G ; van Rij, Andre M ; Voight, Benjamin F ; Wareham, Nick J ; Wells, George A ; Anand, Sonia S ; Wichmann, H-Erich ; Wild, Philipp S ; Willenborg, Christina ; Witteman, Jaqueline CM ; Wright, Benjamin J ; Ye, Shu ; Zeller, Tanja ; Ziegler, Andreas ; Cambien, Francois ; Goodall, Alison H ; Andersen, Karl ; Cupples, L Adrienne ; Quertermous, Thomas ; März, Winfried ; Hengstenberg, Christian ; Blankenberg, Stefan ; Ouwehand, Willem H ; Hall, Alistair S ; Deloukas, Panos ; Thompson, John R ; Stefansson, Kari ; Anderson, Jeffrey L ; Roberts, Robert ; Thorsteinsdottir, Unnur ; O'Donnell, Christopher J ; McPherson, Ruth ; Erdmann, Jeanette ; CARDIoGRAM Consortium, ; Samani, Nilesh J ; Ardissino, Diego ; Ball, Stephen G ; Balmforth, Anthony J ; Barnes, Timothy A ; Becker, Diane M ; Becker, Lewis C ; Berger, Klaus ; Bis, Joshua C ; Boekholdt, S Matthijs ; Boerwinkle, Eric ; Braund, Peter S ; Brown, Morris J ; Burnett, Mary Susan ; Buysschaert, Ian ; Cardiogenics, ; Carlquist, John F

Keywords:

Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, HEART-DISEASE, MYOCARDIAL-INFARCTION, EXPRESSION, VARIANTS, GENETICS, DESIGN, POLYMORPHISMS, METAANALYSIS, CHOLESTEROL, Adult, Aged, Alleles, Case-Control Studies, Coronary Artery Disease, Female, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Cardiogenics, CARDIoGRAM Consortium, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 3001 Agricultural biotechnology, 3102 Bioinformatics and computational biology, 3105 Genetics

Abstract:

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.