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.
Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA. rob@ilya.wustl.edu
Robert
R
Culverhouse
Tsvika
T
Klein
William
W
Shannon
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*