Racial/Ethnic Variation in the Association of Lipid-Related Genetic Variants With Blood Lipids in the US Adult Population

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 US population. Methods and Results-Using data from the second phase (1991)(1992)(1993)(1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a nationally representative survey of the US 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, total cholesterol, triglycerides, total cholesterol/ 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 from each of the 3 major racial/ethnic groups in the United States: non-Hispanic whites (nϭ2296), non-Hispanic blacks (nϭ1699), and Mexican Americans (nϭ1713). 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 (Ͻ67%) than in non-Hispanic blacks (Ͻ44%) or Mexican Americans (Ͻ44%). GRSs were strongly associated with increased lipid levels in each racial/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 GRS, was strongly associated with increased blood lipid measures in all major race/ethnic groups in the United States, which may help in identifying subgroups with a high risk for an unfavorable lipid profile. (Circ Cardiovasc Genet. 2011;4:523-533.)Key Words: nutrition surveys Ⅲ lipids Ⅲ continental population groups Ⅲ ethnology Ⅲ cholesterol Ⅲ genetics Ⅲ risk G enome-wide association studies (GWAS) have successfully identified numerous genetic loci associated with blood lipid levels, which are known risk factors for cardiovascular disease. [1][2][3][4][5][6][7][8] These studies have confirmed some risk loci identified in previous candidate gene and linkage analyses, and they have uncovered a panel of new candidate loci for lipid traits such as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Meta-analyses of GWAS have proven fruitful as well. A recent meta-analysis of blood lipid studies reported significant associations of 95 loci with lipid traits in Ͼ100 000 individuals of European ancestry, most of which had concordant effects in nonEuropean populations. 3 Nevertheless, studies have reported racial/ethnic variation in blood li...

Gender and Single Nucleotide Polymorphisms inMTHFR,BHMT,SPTLC1,CRBP2,CETP, andSCARB1Are Significant Predictors of Plasma Homocysteine Normalized by RBC Folate in Healthy Adult

“…Given these previously established positive outcomes of the rs5882 SNP of CETP on cardiovascular health and reduced risk of memory decline and dementia, it is surprising that our study found an increase in log(nHcy) values with this SNP. However, individual SNPs may have very small effects, but the cumulative effect of many SNPs may help to explain some of the variance in phenotype (43), so understanding the protective role of the rs5882 SNP is of further research interest.…”

Transethnic Genetic-Correlation Estimates from Summary Statistics

“…Like other recent methods based on summary statistics, [10][11][12][13][14][15][16][17][18][19][20][21] our approach supplements summary association data with linkage disequilibrium (LD) information from external reference panels, avoids privacy concerns, and is scalable to hundreds of thousands of individuals and millions of markers. Unlike traditional approaches that focus on the similarity of GWAS results, [22][23][24][25][26] we use the entire spectrum of GWAS associations while accounting for LD to avoid filtering correlated SNPs.…”

Interethnic variation in lipid profiles: implications for underidentification of African–Americans at risk for metabolic disorders

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