Assessing the impact of population stratification on genetic association studies
Assessing the impact of population stratification on genetic association studies
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DOI：
10.1038/ng1333
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发表时间：
2004-04-01
期刊：
影响因子：
30.8
通讯作者：
Altshuler, D
中科院分区：
文献类型：
--
作者：
Freedman, ML;Reich, D;Altshuler, D
群体分层指的是病例和对照之间的等位基因频率的差异，这是由于祖先的系统性差异，而不是基因与疾病的关联。已经有人提出，通过对几十个不连锁的遗传标记进行基因分型，可以控制由于分层而导致的假阳性关联。为了评估分层的经验性，我们分析了11个病例对照和病例队列关联研究的数据。我们没有发现有统计学意义的分层证据，但确实观察到，基于几十个标记的评估缺乏能力来排除中等水平的分层，这可能会在旨在检测适度遗传风险因素的研究中导致假阳性关联。在增加了病例队列研究(最不受分层影响的设计)中的标记和样本数量后，我们发现分层实际上是存在的。我们的结果表明，即使在设计良好的研究中，也可能存在适度的分层。
Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study ( the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.