Abstract
BackgroundA recent, large genome-wide association study (GWAS) of European ancestry individuals has identified multiple genetic variants influencing serum lipids. Studies of the transferability of these associations to African Americans remain few, an important limitation given interethnic differences in serum lipids and the disproportionate burden of lipid-associated metabolic diseases among African Americans.MethodsWe attempted to evaluate the transferability of 95 lipid-associated loci recently identified in European ancestry individuals to 887 non-diabetic, unrelated African Americans from a population-based sample in the Washington, DC area. Additionally, we took advantage of the generally reduced linkage disequilibrium among African ancestry populations in comparison to European ancestry populations to fine-map replicated GWAS signals.ResultsWe successfully replicated reported associations for 10 loci (CILP2/SF4, STARD3, LPL, CYP7A1, DOCK7/ANGPTL3, APOE, SORT1, IRS1, CETP, and UBASH3B). Through trans-ethnic fine-mapping, we were able to reduce associated regions around 75% of the loci that replicated.ConclusionsBetween this study and previous work in African Americans, 40 of the 95 loci reported in a large GWAS of European ancestry individuals also influence lipid levels in African Americans. While there is now evidence that the lipid-influencing role of a number of genetic variants is observed in both European and African ancestry populations, the still considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of these traits.
Highlights
A recent, large genome-wide association study (GWAS) of European ancestry individuals has identified multiple genetic variants influencing serum lipids
Great effort has gone into uncovering the genetic epidemiology of serum lipids, including a recent meta-analysis of 46 genome-wide studies comprising more than 100,000 individuals of European ancestry [1]
We used more robust analytic strategies to investigate the transferability of reported genetic associations for serum lipids to African Americans
Summary
A recent, large genome-wide association study (GWAS) of European ancestry individuals has identified multiple genetic variants influencing serum lipids. Studies of the transferability of these associations to African Americans remain few, an important limitation given interethnic differences in serum lipids and the disproportionate burden of lipid-associated metabolic diseases among African Americans. Great effort has gone into uncovering the genetic epidemiology of serum lipids, including a recent meta-analysis of 46 genome-wide studies comprising more than 100,000 individuals of European ancestry [1]. We used more robust analytic strategies to investigate the transferability of reported genetic associations for serum lipids to African Americans. We exploited these interethnic differences in LD to conduct fine-mapping of the replicated loci
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