Trans-ethnic study design approaches for fine-mapping.
Trans-ethnic study design approaches for fine-mapping.
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DOI：
10.1038/ejhg.2016.1
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发表时间：
2016-08
期刊：
影响因子：
--
通讯作者：
Zeggini E
中科院分区：
文献类型：
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作者：
Asimit JL;Hatzikotoulas K;McCarthy M;Morris AP;Zeggini E
遍历祖先不同群体的研究可能会增加检测新位点的能力，并通过利用种族群体之间的连锁不平衡差异来提高因果变异的精细定位分辨率。由于低连锁不平衡和高遗传异质性，纳入非洲血统样本可能会产生进一步的改进。我们研究了在不同祖先组成（欧洲、东亚、非洲）、等位基因异质性和因果变异次要等位基因频率的情况下，对五个 II 型糖尿病基因座的跨种族固定效应荟萃分析的精细定位分辨率。特别是，比较了祖先组成的三种设置：（1）单一祖先（欧洲），（2）中等祖先多样性（欧洲和东亚），以及（3）高度祖先多样性（欧洲、东亚和非洲）。我们的模拟表明，欧洲/亚洲和仅欧洲血统的荟萃分析始终获得相似的精细映射分辨率。将非洲血统样本纳入荟萃分析可显着提高精细绘图分辨率。
Studies that traverse ancestrally diverse populations may increase power to detect novel loci and improve fine-mapping resolution of causal variants by leveraging linkage disequilibrium differences between ethnic groups. The inclusion of African ancestry samples may yield further improvements because of low linkage disequilibrium and high genetic heterogeneity. We investigate the fine-mapping resolution of trans-ethnic fixed-effects meta-analysis for five type II diabetes loci, under various settings of ancestral composition (European, East Asian, African), allelic heterogeneity, and causal variant minor allele frequency. In particular, three settings of ancestral composition were compared: (1) single ancestry (European), (2) moderate ancestral diversity (European and East Asian), and (3) high ancestral diversity (European, East Asian, and African). Our simulations suggest that the European/Asian and European ancestry-only meta-analyses consistently attain similar fine-mapping resolution. The inclusion of African ancestry samples in the meta-analysis leads to a marked improvement in fine-mapping resolution.