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.

TitleGenetic 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 TypeJournal Article
Year of Publication2010
AuthorsBressler, J, Folsom, AR, Couper, DJ, Volcik, KA, Boerwinkle, E
JournalAm J Epidemiol
Volume171
Issue1
Pagination14-23
Date Published2010 Jan 01
ISSN1476-6256
KeywordsAfrican Americans, Case-Control Studies, Coronary Artery Disease, European Continental Ancestry Group, 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
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.

DOI10.1093/aje/kwp377
Alternate JournalAm. J. Epidemiol.
PubMed ID19955471
PubMed Central IDPMC2800304
Grant ListN01HC55020 / 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
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / 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
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States