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

Am J Epidemiol. 2010 Jan 1;171(1):14-23. doi: 10.1093/aje/kwp377. Epub 2009 Dec 2.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans
  • Case-Control Studies
  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / mortality
  • 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 / epidemiology
  • United States / epidemiology