Serum vitamins A and E as modifiers of lipid trait genetics in the National Health and Nutrition Examination Surveys as part of the Population Architecture using Genomics and Epidemiology (PAGE) study

Hum Genet. 2012 Nov;131(11):1699-708. doi: 10.1007/s00439-012-1186-y. Epub 2012 Jun 12.


Both environmental and genetic factors impact lipid traits. Environmental modifiers of known genotype-phenotype associations may account for some of the "missing heritability" of these traits. To identify such modifiers, we genotyped 23 lipid-associated variants identified previously through genome-wide association studies (GWAS) in 2,435 non-Hispanic white, 1,407 non-Hispanic black, and 1,734 Mexican-American samples collected for the National Health and Nutrition Examination Surveys (NHANES). Along with lipid levels, NHANES collected environmental variables, including fat-soluble macronutrient serum levels of vitamin A and E levels. As part of the Population Architecture using Genomics and Epidemiology (PAGE) study, we modeled gene-environment interactions between vitamin A or vitamin E and 23 variants previously associated with high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. We identified three SNP × vitamin A and six SNP × vitamin E interactions at a significance threshold of p < 2.2 × 10(-3). The most significant interaction was APOB rs693 × vitamin E (p = 8.9 × 10(-7)) for LDL-C levels among Mexican-Americans. The nine significant interaction models individually explained 0.35-1.61% of the variation in any one of the lipid traits. Our results suggest that vitamins A and E may modify known genotype-phenotype associations; however, these interactions account for only a fraction of the overall variability observed for HDL-C, LDL-C, and TG levels in the general population.

Publication types

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

MeSH terms

  • Adult
  • African Americans / genetics
  • Cholesterol, HDL / genetics*
  • Cholesterol, LDL / genetics*
  • Cohort Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Fluorescent Antibody Technique
  • Gene-Environment Interaction*
  • Genetic Association Studies
  • Genetic Markers
  • Genome-Wide Association Study
  • Humans
  • Mexican Americans / genetics
  • Molecular Epidemiology
  • Nutrition Surveys
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait Loci
  • Risk Factors
  • Triglycerides / genetics*
  • Vitamin A / blood*
  • Vitamin E / blood*


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Genetic Markers
  • Triglycerides
  • Vitamin A
  • Vitamin E