Lack of Associations of Ten Candidate Coronary Heart Disease Risk Genetic Variants and Subclinical Atherosclerosis in Four US Populations: The Population Architecture Using Genomics and Epidemiology (PAGE) Study

Atherosclerosis. 2013 Jun;228(2):390-9. doi: 10.1016/j.atherosclerosis.2013.02.038. Epub 2013 Mar 13.

Abstract

Background: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque.

Methods: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model.

Results: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR = 1.32, 95% confidence interval: 1.17, 1.49, P = 1.08 × 10(-5)), but not in the other populations (P = 0.90 in EA and P = 0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR = 1.07, P = 0.02) and in AI (OR = 1.10, P = 0.05).

Conclusions: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans / genetics
  • Aged
  • Ankle Brachial Index
  • Asymptomatic Diseases
  • Carotid Artery Diseases / diagnosis
  • Carotid Artery Diseases / epidemiology*
  • Carotid Artery Diseases / ethnology
  • Carotid Artery Diseases / genetics*
  • Carotid Intima-Media Thickness
  • Coronary Disease / diagnosis
  • Coronary Disease / epidemiology*
  • Coronary Disease / ethnology
  • Coronary Disease / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Indians, North American / genetics
  • Linear Models
  • Logistic Models
  • Male
  • Mexican Americans / genetics
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology

Grant support