Title | Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the atherosclerosis risk in communities study. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Bressler, J, Folsom, AR, Couper, DJ, Volcik, KA, Boerwinkle, E |
Journal | Am J Epidemiol |
Volume | 171 |
Issue | 1 |
Pagination | 14-23 |
Date Published | 2010 Jan 01 |
ISSN | 1476-6256 |
Keywords | Black or African American, Case-Control Studies, Coronary Artery Disease, Female, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Residence Characteristics, Risk, Risk Assessment, Risk Factors, United Kingdom, United States, White People |
Abstract | In 2007, the Wellcome Trust Case Control Consortium (WTCCC) performed a genome-wide association study in 2,000 British coronary heart disease (CHD) cases and 3,000 controls after genotyping 469,557 single nucleotide polymorphisms (SNPs). Seven variants associated with CHD were initially identified, and 5 SNPs were later found in replication studies. In the current study, the authors aimed to determine whether the 12 SNPs reported by the WTCCC predicted incident CHD through 2004 in a biracial, prospective cohort study (Atherosclerosis Risk in Communities) comprising 15,792 persons aged 45-64 years who had been selected by probability sampling from 4 different US communities in 1987-1989. Cox proportional hazards models with adjustment for age and gender were used to estimate CHD hazard rate ratios (HRRs) over a 17-year period (1,362 cases in whites and 397 cases in African Americans) under an additive genetic model. The results showed that 3 SNPs in whites (rs599839, rs1333049, and rs501120; HRRs were 1.10 (P = 0.044), 1.14 (P < 0.001), and 1.14 (P = 0.030), respectively) and 1 SNP in African Americans (rs7250581; HRR = 1.60, P = 0.05) were significantly associated with incident CHD. This study demonstrates that genetic variants revealed in a case-control genome-wide association study enriched for early disease onset may play a role in the genetic etiology of CHD in the general population. |
DOI | 10.1093/aje/kwp377 |
Alternate Journal | Am J Epidemiol |
PubMed ID | 19955471 |
PubMed Central ID | PMC2800304 |
Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States |
Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the atherosclerosis risk in communities study.
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