title: A new statistical screening approach for finding pharmacokinetics-related genes in genome-wide studies.
abstract: 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.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: N M
authors.initials: NM
authors.lastname: Laird
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Hamano
authors.forename: A
authors.initials: A
authors.lastname: Yafune
authors.forename: N
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: E
authors.initials: E
authors.lastname: Sugiyama
authors.forename: S-R
authors.initials: SR
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Furuse
authors.forename: H
authors.initials: H
authors.lastname: Ishii
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
authors.forename: N
authors.initials: N
authors.lastname: Saijo
authors.forename: J-I
authors.initials: JI
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D003198:Computer Simulation; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D009010:Monte Carlo Method; D010597:Pharmacogenetics / Q000706:statistics & numerical data*; D010599:Pharmacokinetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide