Race/Ethnic Variation in the Association of Lipid-Related Genetic Variants with Blood Lipids in the Adult U.S. Population.

Chang MH, Ned RM, Hong Y, Yesupriya A, Yang Q, Liu T, Janssens AC, Dowling NF.

Source

1 Centers for Disease Control and Prevention, Atlanta, GA;

Abstract

BACKGROUND:

-Genome-wide association studies (GWAS) have identified a number of single nucleotide polymorphisms (SNPs) associated with serum lipid level in populations of European descent. The individual and the cumulative effect of these SNPs on blood lipids are largely unclear for the U.S. population.

METHODS AND RESULTS:

-Using data from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a nationally-representative survey of the U.S. population, we examined associations of 57 GWAS-identified or well-established lipid-related genetic loci with plasma concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), TC/HDL-C ratio, and non-HDL-C. We used multivariable linear regression to examine single SNP associations and the cumulative effect of multiple SNPs (using a genetic risk score, GRS) on blood lipid levels. Analyses were conducted in adults for each of the three major racial/ethnic groups in the U.S.: non-Hispanic whites (n = 2,296), non-Hispanic blacks (n = 1,699), and Mexican Americans (n = 1,713). Allele frequencies for all SNPs varied significantly by race/ethnicity, except rs3764261 in CETP. Individual SNPs had very small effects on lipid levels, effects that were generally consistent in direction across racial/ethnic groups. More GWAS-validated SNPs were replicated in non-Hispanic whites (< 67%) than in non-Hispanic blacks (< 44%) or Mexican Americans (< 44%). Genetic risk scores were strongly associated with increased lipid levels in each race/ethnic group. The combination of all SNPs into a weighted GRS explained no more than 11% of the total variance in blood lipid levels.

CONCLUSIONS:

-Our findings show that the combined association of SNPs, based on a genetic risk score, was strongly associated with increased blood lipid measures in all major race/ethnic groups in the U.S., which may help in identifying subgroups with a high risk for an unfavorable lipid profile.