A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies
A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies
复制标题
在全基因组研究中寻找药代动力学相关基因的新统计筛选方法
DOI：
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
T. Yoshida
中科院分区：
文献类型：
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作者：
Yasunori Sato;Nan M. Laird;Kengo Nagashima;R. Kato;T. Hamano;A. Yafune;N. Kaniwa;Yoshiro Saito;E. Sugiyama;S;J. Furuse;H. Ishii;H. Ueno;T. Okusaka;Nagahiro Saijo;J. Sawada;T. Yoshida
生物医学研究者通常通过Kruskal-Wallis检验检验零假设，即基因型之间的药代动力学（PK）参数的群体平均值没有差异。尽管PK相关基因预期具有多个等位基因的单调递增模式，但Kruskal-Wallis检验未考虑单调响应模式。为了在临床和毒理学试验中检测这种模式，已经提出了最大对比度方法。我们展示了该方法如何与药物基因组学数据一起使用，以开发相关性测试。此外，使用模拟研究，我们比较的功率的修改后的最大对比度方法的最大对比度方法和Kruskal-Wallis检验。根据这些研究的结果，我们提出了在特定情况下使用统计数据的经验法则。所有这三种方法的应用，以实际的全基因组药物基因组学研究说明了我们的讨论的实际意义。
Biomedical researchers usually test the null hypothesis that there is no difference of the population mean of pharmacokinetics (PK) parameters between genotypes by the Kruskal–Wallis test. Although a monotone increasing pattern with a number of alleles is expected for PK-related genes, the Kruskal–Wallis test does not consider a monotonic response pattern. For detecting such patterns in clinical and toxicological trials, a maximum contrast method has been proposed. We show how that method can be used with pharmacogenomics data to a develop test of association. Further, using simulation studies, we compare the power of the modified maximum contrast method to those of the maximum contrast method and the Kruskal–Wallis test. On the basis of the results of those studies, we suggest rules of thumb for which statistics to use in a given situation. An application of all three methods to an actual genome-wide pharmacogenomics study illustrates the practical relevance of our discussion.