Human Genetics

, Volume 131, Issue 11, pp 1699–1708

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

Authors

  • Logan Dumitrescu
    • Center for Human Genetics ResearchVanderbilt University
  • Robert Goodloe
    • Center for Human Genetics ResearchVanderbilt University
  • Kristin Brown-Gentry
    • Center for Human Genetics ResearchVanderbilt University
  • Ping Mayo
    • Center for Human Genetics ResearchVanderbilt University
  • Melissa Allen
    • Center for Human Genetics ResearchVanderbilt University
  • Hailing Jin
    • Center for Human Genetics ResearchVanderbilt University
  • Niloufar B. Gillani
    • Center for Human Genetics ResearchVanderbilt University
  • Nathalie Schnetz-Boutaud
    • Center for Human Genetics ResearchVanderbilt University
  • Holli H. Dilks
    • Center for Human Genetics ResearchVanderbilt University
    • Department of Molecular Physiology and BiophysicsVanderbilt University
    • Center for Human Genetics ResearchVanderbilt University
    • Department of Molecular Physiology and BiophysicsVanderbilt University
Original Investigation

DOI: 10.1007/s00439-012-1186-y

Cite this article as:
Dumitrescu, L., Goodloe, R., Brown-Gentry, K. et al. Hum Genet (2012) 131: 1699. doi:10.1007/s00439-012-1186-y

Abstract

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.

Supplementary material

439_2012_1186_MOESM1_ESM.docx (36 kb)
Supplementary material 1 (DOCX 35 kb)

Copyright information

© Springer-Verlag 2012