Fine-mapping in African Americans of 8 recently discovered genetic loci for plasma lipids: the Jackson Heart Study

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Resource Type

Properties

1. Additional Topic(s)

   Genetic association of lipid traits

2. Additional Topic(s)

   Single Nucleotide Polymorphism

3. Resource Description

   Abstract 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.

4. Contact

   Taylor, Jr., Herman A.

5. PI

   Taylor, Jr., Herman A.

6. Topic

   lipid metabolism disorder

7. Study Population

   4,605 African Americans

8. Related Publication or Documentation

   Fine-mapping in African Americans of 8 recently discovered genetic loci for plasma lipids: the Jackson Heart Study.

9. Funded by

   National Heart, Lung, and Blood Institute

10. Performed by

    Jackson Heart Study