Trans-ethnic genome-wide association studies: advantages and challenges of mapping in diverse populations.
Trans-ethnic genome-wide association studies: advantages and challenges of mapping in diverse populations.
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DOI：
10.1186/s13073-014-0091-5
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发表时间：
2014
期刊：
影响因子：
12.3
通讯作者：
Keating BJ
中科院分区：
文献类型：
--
作者：
Li YR;Keating BJ
全基因组关联研究（GWAS）是遗传学家最常用于询问人类基因组的方法，它们提供了一种具有成本效益的方法来识别支持复杂性状和疾病的遗传变异。鉴于少数民族样本有限，大多数最初的GWAS侧重于欧洲人口的遗传同质群体，以限制人口分层效应。跨种族研究在解释常见数量性状（如身高）的遗传性和检查复杂疾病（如2型糖尿病）的遗传结构方面具有非常宝贵的价值。它们为独立人群中的大规模信号复制和跨人群荟萃分析提供了机会，以提高统计功效。此外，跨种族GWAS能够优先考虑候选基因，功能变体的精细定位，并通过利用不同种族人群之间基因组连锁不平衡的自然差异，潜在地识别与混合人群中疾病风险相关的SNP。最近的努力，以评估GWAS确定的变异的生物学功能，强调了需要大规模的复制，荟萃分析和精细映射在世界各地的种族不同的遗传祖先的人群。在这里，我们回顾了最新的进展和新的方法，重要的是要考虑执行时，设计或解释跨种族GWAS，我们强调现有的挑战，如有限的能力来处理异质性的连锁不平衡的人群和限制在解剖复杂的架构，如最近发现的混合人口。本文的在线版本（doi：10.1186/s13073-014-0091-5）包含补充材料，可供授权用户使用。
Genome-wide association studies (GWASs) are the method most often used by geneticists to interrogate the human genome, and they provide a cost-effective way to identify the genetic variants underpinning complex traits and diseases. Most initial GWASs have focused on genetically homogeneous cohorts from European populations given the limited availability of ethnic minority samples and so as to limit population stratification effects. Transethnic studies have been invaluable in explaining the heritability of common quantitative traits, such as height, and in examining the genetic architecture of complex diseases, such as type 2 diabetes. They provide an opportunity for large-scale signal replication in independent populations and for cross-population meta-analyses to boost statistical power. In addition, transethnic GWASs enable prioritization of candidate genes, fine-mapping of functional variants, and potentially identification of SNPs associated with disease risk in admixed populations, by taking advantage of natural differences in genomic linkage disequilibrium across ethnically diverse populations. Recent efforts to assess the biological function of variants identified by GWAS have highlighted the need for large-scale replication, meta-analyses and fine-mapping across worldwide populations of ethnically diverse genetic ancestries. Here, we review recent advances and new approaches that are important to consider when performing, designing or interpreting transethnic GWASs, and we highlight existing challenges, such as the limited ability to handle heterogeneity in linkage disequilibrium across populations and limitations in dissecting complex architectures, such as those found in recently admixed populations. The online version of this article (doi:10.1186/s13073-014-0091-5) contains supplementary material, which is available to authorized users.
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影响因子：
6.9
作者：
Basu, Analabha;Tang, Hua;Arnett, Donna;Gu, C. Charles;Mosley, Tom;Kardia, Sharon;Luke, Amy;Tayo, Bamidele;Cooper, Richard;Zhu, Xiaofeng;Risch, Neil
通讯作者：
Risch, Neil
影响因子：
3.7
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Elbers CC;Guo Y;Tragante V;van Iperen EP;Lanktree MB;Castillo BA;Chen F;Yanek LR;Wojczynski MK;Li YR;Ferwerda B;Ballantyne CM;Buxbaum SG;Chen YD;Chen WM;Cupples LA;Cushman M;Duan Y;Duggan D;Evans MK;Fernandes JK;Fornage M;Garcia M;Garvey WT;Glazer N;Gomez F;Harris TB;Halder I;Howard VJ;Keller MF;Kamboh MI;Kooperberg C;Kritchevsky SB;LaCroix A;Liu K;Liu Y;Musunuru K;Newman AB;Onland-Moret NC;Ordovas J;Peter I;Post W;Redline S;Reis SE;Saxena R;Schreiner PJ;Volcik KA;Wang X;Yusuf S;Zonderland AB;Anand SS;Becker DM;Psaty B;Rader DJ;Reiner AP;Rich SS;Rotter JI;Sale MM;Tsai MY;Borecki IB;Hegele RA;Kathiresan S;Nalls MA;Taylor HA Jr;Hakonarson H;Sivapalaratnam S;Asselbergs FW;Drenos F;Wilson JG;Keating BJ
通讯作者：
Keating BJ
影响因子：
7
作者：
Eskin, Eleazar
通讯作者：
Eskin, Eleazar
影响因子：
1.7
作者：
Adeyemo, A.;Rotimi, C.
通讯作者：
Rotimi, C.
影响因子：
3.5
作者：
Basu, Analabha;Tang, Hua;Risch, Neil J.
通讯作者：
Risch, Neil J.