A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies

作者：Sato Y; Laird N M; Nagashima K; Kato R; Hamano T; Yafune A; Kaniwa N; Saito Y; Sugiyama E; Kim S R; Furuse J; Ishii H; Ueno H; Okusaka T; Saijo N; Sawada J i; Yoshida T^*

来源：The Pharmacogenomics Journal, 2009, 9(2): 137-146.

DOI：10.1038/tpj.2008.17

• gemcitabine
• genome-wide study
• maximum contrast method
• pharmacokinetics-related gene
• statistical screening method

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.

• 出版日期2009-4