TY - JOUR
T1 - Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: Two genome-wide association studies
AU - Myocardial Infarction Genetics Consortium
AU - Wellcome Trust Case Control Consortium
AU - Reilly, Muredach P.
AU - Li, Mingyao
AU - He, Jing
AU - Ferguson, Jane F.
AU - Stylianou, Ioannis M.
AU - Mehta, Nehal N.
AU - Burnett, Mary Susan
AU - Devaney, Joseph M.
AU - Knouff, Christopher W.
AU - Thompson, John R.
AU - Horne, Benjamin D.
AU - Stewart, Alexandre F.R.
AU - Assimes, Themistocles L.
AU - Wild, Philipp S.
AU - Allayee, Hooman
AU - Nitschke, Patrick Linsel
AU - Patel, Riyaz S.
AU - Martinelli, Nicola
AU - Girelli, Domenico
AU - Quyyumi, Arshed A.
AU - Anderson, Jeffrey L.
AU - Schunkert, Heribert
AU - Hall, Alistair S.
AU - Schunkert, Heribert
AU - Quertermous, Thomas
AU - Blankenberg, Stefan
AU - Hazen, Stanley L.
AU - Roberts, Robert
AU - Kathiresan, Sekar
AU - Samani, Nilesh J.
AU - Epstein, Stephen E.
AU - Rader, Daniel J.
PY - 2011/1/29
Y1 - 2011/1/29
N2 - We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We 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). In 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. Our 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. The 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.
AB - We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We 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). In 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. Our 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. The 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.
UR - http://www.scopus.com/inward/record.url?scp=79251619566&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(10)61996-4
DO - 10.1016/S0140-6736(10)61996-4
M3 - Journal articles
AN - SCOPUS:79251619566
SN - 0140-6736
VL - 377
SP - 383
EP - 392
JO - The Lancet
JF - The Lancet
IS - 9763
ER -
