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

BMC Medical Genetics

Research Article

Adebowale Adeyemo¹  Guanjie Chen¹  Ayo P Doumatey¹  Jie Zhou¹  Charles N Rotimi¹  Amy R Bentley¹  Daniel Shriner¹  Hanxia Huang¹  Norman P Gerry²  Michael F Christman²  Alan Herbert³  Katherine G Meilleur⁴ 

[1] Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;Coriell Institute for Medical Research, Camden, NJ, USA;Department of Genetics and Genomics, Boston University, Boston, MA, USA;National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA;

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

DOI  :  10.1186/1471-2350-13-88

 received in 2012-03-05, accepted in 2012-09-11,  发布年份 2012

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Adeyemo et al.; licensee BioMed Central Ltd. 2012