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
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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. / Reilly, Muredach P; Li, Mingyao; He, Jing; Ferguson, Jane F; Stylianou, Ioannis M; Mehta, Nehal N; Burnett, Mary Susan; Devaney, Joseph M; Knouff, Christopher W; Thompson, John R; Horne, Benjamin D; Stewart, Alexandre F R; Assimes, Themistocles L; Wild, Philipp S; Allayee, Hooman; Nitschke, Patrick Linsel; Patel, Riyaz S; Martinelli, Nicola; Girelli, Domenico; Quyyumi, Arshed A; Anderson, Jeffrey L; Erdmann, Jeanette; Hall, Alistair S; Schunkert, Heribert; Quertermous, Thomas; Blankenberg, Stefan; Hazen, Stanley L; Roberts, Robert; Kathiresan, Sekar; Samani, Nilesh J; Epstein, Stephen E; Rader, Daniel J; Myocardial Infarction Genetics Consortium.
in: LANCET, Jahrgang 377, Nr. 9763, 29.01.2011, S. 383-392.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 - 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 - Erdmann, Jeanette
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
AU - Myocardial Infarction Genetics Consortium
N1 - Copyright © 2011 Elsevier Ltd. All rights reserved.
PY - 2011/1/29
Y1 - 2011/1/29
N2 - BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.METHODS: 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).FINDINGS: 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.INTERPRETATION: 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.FUNDING: 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 - BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis.METHODS: 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).FINDINGS: 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.INTERPRETATION: 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.FUNDING: 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.
KW - ABO Blood-Group System/genetics
KW - ADAM Proteins/genetics
KW - ADAMTS7 Protein
KW - Adult
KW - Aged
KW - Coronary Angiography
KW - Coronary Artery Disease/blood
KW - Female
KW - Gene Frequency
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Humans
KW - Linkage Disequilibrium
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/blood
KW - Polymorphism, Single Nucleotide
U2 - 10.1016/S0140-6736(10)61996-4
DO - 10.1016/S0140-6736(10)61996-4
M3 - SCORING: Journal article
C2 - 21239051
VL - 377
SP - 383
EP - 392
JO - LANCET
JF - LANCET
SN - 0140-6736
IS - 9763
ER -