Association of blood lipids with common DNA sequence variants at 19 genetic loci in the multiethnic United States National Health and Nutrition Examination Survey III.
- Authors
- Keebler, Mary E; Sanders, Christopher L; Surti, Aarti; Guiducci, Candace; Burtt, Noel P; Kathiresan, Sekar
- Year
- 2009
- Journal
- Circulation. Cardiovascular genetics
- PMID
- 20031591
- DOI
- 10.1161/CIRCGENETICS.108.829473
- PMCID
- PMC3561731
BACKGROUND: Using the genome-wide association approach in individuals of European ancestry, we and others recently identified single-nucleotide polymorphisms (SNPs) at 19 loci as associated with blood lipids; 8 of these loci were novel. Whether these same SNPs associate with lipids in a broader range of ethnicities is unknown. METHODS AND RESULTS: We genotyped index SNPs at 19 loci in the Third United States National Health and Nutrition Examination Survey (n=7159), a population-based probability sample of the United States comprised primarily of non-Hispanic blacks, Mexican Americans, and non-Hispanic whites. We constructed ethnic-specific residual blood lipid levels after adjusting for age and gender. Ethnic-specific linear regression was used to test the association of genotype with blood lipids. To summarize the statistical evidence across 3 racial groups, we conducted a fixed-effects variance-weighted meta-analysis. After exclusions, there were 1627 non-Hispanic blacks, 1659 Mexican Americans, and 2230 non-Hispanic whites. At 5 loci (1p13 near CELSR2/PSRC1/SORT1, HMGCR, CETP, LPL, and APOA5), the index SNP was associated with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides in all 3 ethnic groups. At the remaining loci, there was mixed evidence by ethnic group. In meta-analysis, we found that, at 14 of the 19 loci, SNPs exceeded a nominal P<0.05. CONCLUSIONS: At 5 loci including the recently discovered region on 1p13 near CELSR2/PSRC1/SORT1, the same SNP discovered in whites associates with blood lipids in non-Hispanic blacks and Mexican Americans. For the remaining loci, fine mapping and resequencing will be required to definitively evaluate the relevance of each locus in individuals of African and Hispanic ancestries.
LDL cholesterol by rs646776 genotype at 1p13LDL cholesterol concentration decreases as the modeled allele copy number increases in non-Hispanic blacks (panel A), non-Hispanic whites (panel B), and Mexican Americans (panel C).
LLM interpretation
This figure consists of three bar charts (panels A, B, and C) showing LDL cholesterol concentrations across three rs646776 genotypes (AA, AG, and GG). In all three panels, the y-axis represents LDL cholesterol levels and the x-axis represents the genotype, with a visible trend of decreasing cholesterol concentrations as the genotype shifts from AA to GG. Error bars are present for each bar, indicating variability within the groups.
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