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. 2012 Sep 21:13:88.
doi: 10.1186/1471-2350-13-88.

Transferability and fine mapping of genome-wide associated loci for lipids in African Americans

Adebowale Adeyemo  1 , Amy R Bentley, Katherine G Meilleur, Ayo P Doumatey, Guanjie Chen, Jie Zhou, Daniel Shriner, Hanxia Huang, Alan Herbert, Norman P Gerry, Michael F Christman, Charles N Rotimi
Affiliations

Transferability and fine mapping of genome-wide associated loci for lipids in African Americans

Adebowale Adeyemo et al. BMC Med Genet. .

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.

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Figures

Figure 1
Figure 1
Summary of methods.
Figure 2
Figure 2
Fine mapping of rs12678919. LocusZoom output for the association of rs12678919 and TG, showing the association of nearby LPL SNP rs1267934, as well.
Figure 3
Figure 3
Fine mapping of rs2081687. LocusZoom output for the association of rs2081687 and LDL, showing the stronger association of nearby SNP rs10088541.
Figure 4
Figure 4
Fine Mapping of rs629301. Comparison of the haplotype structure in the region surrounding rs629301 (marked by an arrow) in the CEU (A) and the YRI (B).
See this image and copyright information in PMC

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