Journal
LANCET
Volume 377, Issue 9763, Pages 383-392Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0140-6736(10)61996-4
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Funding
- Cardiovascular Institute of the University of Pennsylvania
- MedStar Health Research Institute at Washington Hospital Center
- GlaxoSmithKline
- MRC [G0800759, G0600329, G0800675] Funding Source: UKRI
- Medical Research Council [G0800759, G0600329, G0801418B, G0800675, G9817803B] Funding Source: researchfish
- Chief Scientist Office [CZB/4/540] Funding Source: researchfish
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000454] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [U54RR020278, KL2RR024132] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL087647, R01HL071878, K23HL097151, P01HL076491, R01HL087676, P01HL098055] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK071224] Funding Source: NIH RePORTER
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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=12393) 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=4.98x10(-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=7.62x10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group 0 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.
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