title: 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.
  
  
  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 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 (n=2296), non-Hispanic blacks (n=1699), and Mexican Americans (n=1713). 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%). 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.
authors.affiliation: Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. mchang@cdc.gov
authors.forename: Man-huei
authors.initials: MH
authors.lastname: Chang
authors.forename: Renée M
authors.initials: RM
authors.lastname: Ned
authors.forename: Yuling
authors.initials: Y
authors.lastname: Hong
authors.forename: Ajay
authors.initials: A
authors.lastname: Yesupriya
authors.forename: Quanhe
authors.initials: Q
authors.lastname: Yang
authors.forename: Tiebin
authors.initials: T
authors.lastname: Liu
authors.forename: A Cecile J W
authors.initials: AC
authors.lastname: Janssens
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Dowling
mesh_terms: D044383:Black People / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D009749:Nutrition Surveys; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides