Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

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

Nat Genet 2011 Mar 6;43(4):333-8. Epub 2011 Mar 6.

Universität zu Lübeck, Medizinische Klinik II, Lübeck, Germany.

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.

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http://dx.doi.org/10.1038/ng.784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119261PMC
March 2011
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