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.
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.
Center for Human Genetics Research, Vanderbilt University, 2215 Garland Avenue, 515B Light Hall, Nashville, TN 37232, USA. logan.dumitrescu@chgr.mc.vanderbilt.edu
Logan
L
Dumitrescu
Robert
R
Goodloe
Kristin
K
Brown-Gentry
Ping
P
Mayo
Melissa
M
Allen
Hailing
H
Jin
Niloufar B
NB
Gillani
Nathalie
N
Schnetz-Boutaud
Holli H
HH
Dilks
Dana C
DC
Crawford
D000328:Adult; D001741:Black or African American / Q000235:genetics; D008076:Cholesterol, HDL / Q000235:genetics*; D008078:Cholesterol, LDL / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D017058:Mexican Americans / Q000235:genetics; D017720:Molecular Epidemiology; D009749:Nutrition Surveys; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci; D012307:Risk Factors; D014280:Triglycerides / Q000235:genetics*; D014801:Vitamin A / Q000097:blood*; D014810:Vitamin E / Q000097:blood*; D044465:White People / Q000235:genetics
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005819:Genetic Markers; D014280:Triglycerides; D014801:Vitamin A; D014810:Vitamin E