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Open Access Research article

Transferability and Fine Mapping of genome-wide associated loci for lipids in African Americans

Adebowale Adeyemo1*, Amy R Bentley1, Katherine G Meilleur2, Ayo P Doumatey1, Guanjie Chen1, Jie Zhou1, Daniel Shriner1, Hanxia Huang1, Alan Herbert3, Norman P Gerry4, Michael F Christman4 and Charles N Rotimi1*

Author Affiliations

1 Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA

2 National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

3 Department of Genetics and Genomics, Boston University, Boston, MA, USA

4 Coriell Institute for Medical Research, Camden, NJ, USA

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BMC Medical Genetics 2012, 13:88  doi:10.1186/1471-2350-13-88

Published: 21 September 2012

Abstract

Background

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.

Methods

We 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.

Results

We 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.

Conclusions

Between 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.

Keywords:
Lipids; Genetics; African Americans; Genome-wide association study; Ethnicity