Case-control association studies in mixed populations: correcting using genomic control.
Case-control association studies in mixed populations: correcting using genomic control.
复制标题
混合人群中的病例对照关联研究：使用基因组控制进行校正。
DOI：
10.1159/000083541
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Greenberg,DavidA
中科院分区：
文献类型：
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作者：
Shmulewitz,Dvora;Zhang,Junying;Greenberg,DavidA
目的：在混合人群中进行病例对照关联研究，如果亚群疾病患病率和标志物频率均不同，则可能导致虚假的疾病标志物关联。基因组控制（GC）使用中性位点，以纠正虚假的关联（由于人口分层），但如何以及这一工程仍然undertaked.Methods：我们模拟和混合人口不同的疾病和标记频率，但没有标记疾病的关联。结果：随着亚群患病率和标志物差异的增加，校正结果趋于保守（假阳性率<5%）。在平均亚群等位基因频率差异<0.26时，平均校正导致FPR接近5%，但仅包括几个具有大频率差异的标记物导致保守的FPR。从中位数校正FPRs大多是保守的，但成为反保守的几个标志物时，具有较大的频率差异被included.Conclusion：GC都可以导致显着的损失的权力，以检测一个真正的协会（保守）在许多情况下，或可能无法消除虚假的协会（反保守）。在某些情况下，平均校正因子对校正人口分层是有用的，但很难知道这些情况何时存在。
Objective:Case-control association studies in mixed populations can result in spurious disease-marker associations if subpopulation disease prevalence and marker frequencies both differ. Genomic control (GC) uses neutral loci to correct for spurious association (due to population stratification), but how well this works remains undetermined.Methods:We simulated and mixed populations with different disease and marker frequencies but without marker-disease association. We generated case-control datasets, calculated the χ2for disease association with each marker, and applied two GC procedures, dividing by the mean χ2or median-χ2/0.456.Results:Corrections became conservative (false positive rate [FPR] <5%) with increasing subpopulation prevalence and marker differences. The mean correction resulted in FPRs close to 5% at average subpopulation allele frequency differences <0.26, but inclusion of just a few markers with large frequency differences resulted in conservative FPRs. FPRs from the median correction were mostly conservative but became anticonservative when a few markers with large frequency differences were included.Conclusion:GC can both lead to a notable loss of power to detect a true association (conservative) in many circumstances or may fail to eliminate the spurious associations (anticonservative). The mean correction factor is useful in certain situations to correct population stratification, but it is difficult to know when those situations exist.