Genome‐wide contribution of genotype by environment interaction to blood lipid variation

Abstract

How important is genotype by environment interaction (GxE) in human disease risk? Using the tool for Genome‐wide Complex Trait Analysis, we have examined 16 major nutrients and lifestyles, designated as E factors, for their interactions with the genome influencing four blood lipids at the genome‐wide level among 406 men and 414 women in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Based on the estimated GxE variances, we identified several major E factors that contribute significant GxE variance to the total variance of lipid traits in this population: carbohydrates for total cholesterol, alcohol use and total fat intake for HDL‐C, and polyunsaturated fat intake for triglycerides. We then performed genome‐wide association study (GWAS) for the most significant E factor and one nonsignificant E factor and identified a set of SNPs showing GxE interactions for each lipid trait. GWAS results further support significant contribution of GxE interaction in blood lipid variation. In summary, we demonstrated a novel approach to determine to what extent GxE contributes to the variations of blood lipids and which specific factors are important for a given risk factor at the genome‐wide level. These findings provide basic evidence on how important genotypes by diet and lifestyle interaction contribute to CVD risk.