期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 3, 期 4, 页码 358-U149出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.109.914267
关键词
lipids; genetics; epidemiology; risk factors
资金
- NHLBI NIH HHS [R01 HL084107-01, N01HC95171, N01-HC-95172, N01-HC-95171, R01-HL-084107, N01-HC-95170, K23 HL083102, K08 HL098361-02, N01 HC095171, N01 HC095170, N01HC95172, K08 HL098361, K23 HL083102-01A1, N01HC95170, R01 HL084107, K08 HL098361-01A1, N01 HC095172] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007753] Funding Source: Medline
Background-Genome-wide association studies in cohorts of European descent have identified novel genomic regions as associated with lipids, but their relevance in African Americans remains unclear. Methods and Results-We genotyped 8 index single nucleotide polymorphisms (SNPs) and 488 tagging SNPs across 8 novel lipid loci in the Jackson Heart Study, a community-based cohort of 4605 African Americans. For each trait, we calculated residuals adjusted for age, sex, and global ancestry and performed multivariable linear regression to detect genotype-phenotype association with adjustment for local ancestry. To explore admixture effects, we conducted stratified analyses in individuals with a high probability of 2 African ancestral alleles or at least 1 European allele at each locus. We confirmed 2 index SNPs as associated with lipid traits in African Americans, with suggestive association for 3 more. However, the effect sizes for 4 of the 5 associated SNPs were larger in the European local ancestry subgroup compared with the African local ancestry subgroup, suggesting that the replication is driven by European ancestry segments. Through fine-mapping, we discovered 3 new SNPs with significant associations, 2 with consistent effect on triglyceride levels across ancestral groups: rs636523 near DOCK7/ANGPTL3 and rs780093 in GCKR. African linkage disequilibrium patterns did not assist in narrowing association signals. Conclusions-We confirm that 5 genetic regions associated with lipid traits in European-derived populations are relevant in African Americans. To further evaluate these loci, fine-mapping in larger African American cohorts and/or resequencing will be required. (Circ Cardiovasc Genet. 2010; 3: 358-364.)
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