Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
BMC Med Genet. 2012 Sep 21;13:88. doi: 10.1186/1471-2350-13-88.
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.
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.
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.
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.
最近一项针对欧洲血统个体的大型全基因组关联研究（GWAS）已经确定了多个影响血清脂质的遗传变异。然而，针对这些关联在非裔美国人中的可转移性的研究仍然很少，这是一个重要的局限性，因为非裔美国人和欧洲裔美国人之间的血清脂质存在差异，并且与脂质相关的代谢疾病在非裔美国人中的负担不成比例。
我们试图评估最近在欧洲血统个体中发现的 95 个与脂质相关的基因座在 887 名来自华盛顿特区地区基于人群的样本中的非糖尿病、无关的非裔美国人中的可转移性。此外，我们利用非洲裔人群中与欧洲裔人群相比普遍较低的连锁不平衡，对已复制的 GWAS 信号进行精细映射。
我们成功复制了 10 个基因座（CILP2/SF4、STARD3、LPL、CYP7A1、DOCK7/ANGPTL3、APOE、SORT1、IRS1、CETP 和 UBASH3B）的报道关联。通过跨种族精细映射，我们能够将复制的基因座的相关区域缩小约 75%。
在这项研究和以前在非裔美国人中的工作基础上，在一项针对欧洲血统个体的大型 GWAS 中报告的 95 个基因座中的 40 个也会影响非裔美国人的脂质水平。虽然现在有证据表明，许多遗传变异对脂质的影响在欧洲和非洲裔人群中都存在，但仍然存在相当大的不一致性，这突显了继续进行特定于种族的研究以阐明这些特征的遗传基础的重要性。
