Accounting for ancestry: population substructure and genome-wide association studies
Accounting for ancestry: population substructure and genome-wide association studies
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DOI：
10.1093/hmg/ddn268
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发表时间：
2008-10-15
影响因子：
3.5
通讯作者：
Seldin, Michael F.
中科院分区：
文献类型：
--
作者：
Tian, Chao;Gregersen, Peter K.;Seldin, Michael F.
解释人类群体的遗传子结构已成为研究复杂遗传疾病的一个主要实际问题。在遗传学研究中，种族和亚组之间的等位基因频率差异以及不同种族之间的混合可能导致频繁的假阳性结果或降低功效。本文综述了在定义人群差异和应用统计学方法改进关联研究方面存在的问题和进展。现在可以考虑使用数千个全基因组单核苷酸多态性或选定的祖先信息标记的群体分层的混杂效应。这些方法不需要任何人口统计学信息，因此可以广泛应用于从多个来源获得的基因型。我们进一步建议，这将是重要的，探索结果在同质的人口子集，因为我们试图确定基因组变异影响复杂的表型的程度。
Accounting for the genetic substructure of human populations has become a major practical issue for studying complex genetic disorders. Allele frequency differences among ethnic groups and subgroups and admixture between different ethnic groups can result in frequent false-positive results or reduced power in genetic studies. Here, we review the problems and progress in defining population differences and the application of statistical methods to improve association studies. It is now possible to take into account the confounding effects of population stratification using thousands of unselected genome-wide single-nucleotide polymorphisms or, alternatively, selected panels of ancestry informative markers. These methods do not require any demographic information and therefore can be widely applied to genotypes available from multiple sources. We further suggest that it will be important to explore results in homogeneous population subsets as we seek to define the extent to which genomic variation influences complex phenotypes.