Multiethnic genetic association studies improve power for locus discovery.
Multiethnic genetic association studies improve power for locus discovery.
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DOI：
10.1371/journal.pone.0012600
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发表时间：
2010-09-08
期刊：
影响因子：
3.7
通讯作者：
de Bakker PI
中科院分区：
文献类型：
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作者：
Pulit SL;Voight BF;de Bakker PI
To date, genome-wide association studies have focused almost exclusively on populations of European ancestry. These studies continue with the advent of next-generation sequencing, designed to systematically catalog and test low-frequency variation for a role in disease. A complementary approach would be to focus further efforts on cohorts of multiple ethnicities. This leverages the idea that population genetic drift may have elevated some variants to higher allele frequency in different populations, boosting statistical power to detect an association. Based on empirical allele frequency distributions from eleven populations represented in HapMap Phase 3 and the 1000 Genomes Project, we simulate a range of genetic models to quantify the power of association studies in multiple ethnicities relative to studies that exclusively focus on samples of European ancestry. In each of these simulations, a first phase of GWAS in exclusively European samples is followed by a second GWAS phase in any of the other populations (including a multiethnic design). We find that nontrivial power gains can be achieved by conducting future whole-genome studies in worldwide populations, where, in particular, African populations contribute the largest relative power gains for low-frequency alleles (<5%) of moderate effect that suffer from low power in samples of European descent. Our results emphasize the importance of broadening genetic studies to worldwide populations to ensure efficient discovery of genetic loci contributing to phenotypic trait variability, especially for those traits for which large numbers of samples of European ancestry have already been collected and tested.
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影响因子：
30.8
作者：
Keinan, Alon;Mullikin, James C.;Reich, David
通讯作者：
Reich, David
影响因子：
7
作者：
Clark, AG;Hubisz, MJ;Nielsen, R
通讯作者：
Nielsen, R
影响因子：
30.8
作者：
Steinthorsdottir, Valgerdur;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari
DOI：
10.1126/science.1142364
发表时间：
2007-06-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Zeggini E;Weedon MN;Lindgren CM;Frayling TM;Elliott KS;Lango H;Timpson NJ;Perry JR;Rayner NW;Freathy RM;Barrett JC;Shields B;Morris AP;Ellard S;Groves CJ;Harries LW;Marchini JL;Owen KR;Knight B;Cardon LR;Walker M;Hitman GA;Morris AD;Doney AS;Wellcome Trust Case Control Consortium (WTCCC);McCarthy MI;Hattersley AT
通讯作者：
Hattersley AT
影响因子：
64.8
作者：
通讯作者：
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