• Muredach P Reilly, Mingyao Li, Jing He, Jane F Ferguson, Ioannis M Stylianou, Nehal N Mehta, Mary Susan Burnett, Joseph M Devaney, Christopher W Knouff, John R Thompson, Benjamin D Horne, Stewart Alexandre F R AF, Themistocles L Assimes, Philipp S Wild, Hooman Allayee, Patrick Linsel Nitschke, Riyaz S Patel, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Nicola Martinelli, Domenico Girelli, Arshed A Quyyumi, Jeffrey L Anderson, Jeanette Erdmann, Alistair S Hall, Heribert Schunkert, Thomas Quertermous, Stefan Blankenberg, Stanley L Hazen, Robert Roberts, Sekar Kathiresan, Nilesh J Samani, Stephen E Epstein, and Daniel J Rader.
• Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. muredach@mail.med.upenn.edu
• Lancet. 2011 Jan 29; 377 (9763): 383-92.

BackgroundWe tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.MethodsWe did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644).FindingsIn the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction.InterpretationOur findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD.FundingThe PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.Copyright © 2011 Elsevier Ltd. All rights reserved.

29 keywords...

hide…