Evaluation of association tests for rare variants using simulated data sets in the Genetic Analysis Workshop 17 data.
Evaluation of association tests for rare variants using simulated data sets in the Genetic Analysis Workshop 17 data.
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DOI：
10.1186/1753-6561-5-s9-s86
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Gao G
中科院分区：
文献类型：
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作者：
Chen W;Gao X;Wang J;Sun C;Wan W;Zhi D;Liu N;Chen X;Gao G
我们评估了四个关联测试罕见的变异相结合的多变量和崩溃（CMC）的方法，两个加权和的方法，和一个变量阈值的方法，通过将它们应用到模拟数据集的遗传分析研讨会17（GAW 17）数据无关的个人。使用家族错误率（FWER）和平均功效作为评价标准。我们的研究结果表明，当一个基因中的所有非同义SNP（罕见变异和常见变异）进行联合分析时，CMC方法无法控制FWER;当只分析罕见变异（次要等位基因频率小于0.05的单核苷酸多态性）时，所有四种方法都可以很好地控制FWER。所有四种方法具有相当的功效，对于GAW 17数据集的分析而言，功效较低。其中三种方法（不包括CMC方法）涉及使用置换程序估计p值，这些置换程序可能是计算密集型的或生成膨胀的FWER。我们适应这三种方法的快速置换过程。结果表明，在GAW 17数据集上，使用快速置换过程可以产生接近于标准置换过程所获得的值的FWER和平均功率。标准置换过程是计算密集型的。
We evaluate four association tests for rare variants—the combined multivariate and collapsing (CMC) method, two weighted-sum methods, and a variable threshold method—by applying them to the simulated data sets of unrelated individuals in the Genetic Analysis Workshop 17 (GAW17) data. The family-wise error rate (FWER) and average power are used as criteria for evaluation. Our results show that when all nonsynonymous SNPs (rare variants and common variants) in a gene are jointly analyzed, the CMC method fails to control the FWER; when only rare variants (single-nucleotide polymorphisms with minor allele frequency less than 0.05) are analyzed, all four methods can control FWER well. All four methods have comparable power, which is low for the analysis of the GAW17 data sets. Three of the methods (not including the CMC method) involve estimation of p-values using permutation procedures that either can be computationally intensive or generate inflated FWERs. We adapt a fast permutation procedure into these three methods. The results show that using the fast permutation procedure can produce FWERs and average powers close to the values obtained from the standard permutation procedure on the GAW17 data sets. The standard permutation procedure is computationally intensive.