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.