Detecting epistatic interactions contributing to quantitative traits.
The restricted partition method (RPM) is a partitioning algorithm for examining multi-locus genotypes as (potentially non-additive) predictors of a quantitative trait. The motivating application was to develop a robust method to examine quantitative phenotypes for epistasis (gene-gene interactions), but the method can be applied without modification to gene-environment interactions. Simulation results indicate that the method provides an efficient way to identify loci contributing epistatically to a quantitative trait, even if the loci have no single locus effects. Statistical significance can be estimated through permutation testing. An example using real data involving the metabolism of a chemotherapy drug is included for illustration. Although the examples in this article involve 2-locus interactions, the RPM is computationally feasible for the analysis of more than two loci or factors.
Culverhouse
Robert
R
Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA. rob@ilya.wustl.edu
Klein
Tsvika
T
Shannon
William
W
D000465:Algorithms; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D040641:Quantitative Trait Loci / Q000235:genetics*