Quantification of the power of Hardy-Weinberg equilibrium testing to detect genotyping error
Quantification of the power of Hardy-Weinberg equilibrium testing to detect genotyping error
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DOI：
10.1159/000091787
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发表时间：
2006-01-01
期刊：
影响因子：
1.8
通讯作者：
Kraft, P
中科院分区：
文献类型：
--
作者：
Cox, DG;Kraft, P
偏离Hardy-Weinberg平衡已成为基因分型错误的公认检验。虽然人们普遍认为，测试偏离哈迪-温伯格平衡检测基因分型错误是不敏感的，很少有人做量化这种敏感性。因此，我们已经检查了基因分型错误的各种模型，包括降低基因分型测定性能的相邻SNP引起的错误。然后，我们计算卡方拟合优度检验偏离Hardy-Weinberg平衡的能力，以检测这种错误。我们还在病例对照关联研究中研究了邻近SNP对风险估计的影响。我们模拟了偏离Hardy-Weinberg平衡的能力，作为检测基因分型错误的检验，并量化了基因分型错误对疾病风险估计的影响。一般来说，基因分型错误不会产生足够的偏离哈迪-温伯格平衡检测。正如预期的那样，由于邻近SNP导致的基因分型错误通常会大幅降低风险估计。目前，最广泛接受的检测基因分型错误的方法是通过测序和/或通过单独的方法进行基因分型来确认基因型。虽然这些方法是相当可靠的，但它们也是昂贵和耗时的。版权所有（c）2006 S. Karger AG，巴塞尔。
Deviation from Hardy-Weinberg equilibrium has become an accepted test for genotyping error. While it is generally considered that testing departures from Hardy-Weinberg equilibrium to detect genotyping error is not sensitive, little has been done to quantify this sensitivity. Therefore, we have examined various models of genotyping error, including error caused by neighboring SNPs that degrade the performance of genotyping assays. We then calculated the power of chi-square goodness-of-fit tests for deviation from Hardy-Weinberg equilibrium to detect such error. We have also examined the affects of neighboring SNPs on risk estimates in the setting of case-control association studies. We modeled the power of departure from Hardy-Weinberg equilibrium as a test to detect genotyping error and quantified the effect of genotyping error on disease risk estimates. Generally, genotyping error does not generate sufficient deviation from Hardy-Weinberg equilibrium to be detected. As expected, genotyping error due to neighboring SNPs attenuates risk estimates, often drastically. For the moment, the most widely accepted method of detecting genotyping error is to confirm genotypes by sequencing and/or genotyping via a separate method. While these methods are fairly reliable, they are also costly and time consuming. Copyright (c) 2006 S. Karger AG, Basel.