A comparison of internal model validation methods for multifactor dimensionality reduction in the case of genetic heterogeneity

Jeffrey J Gory, Holly C Sweeney, David M Reif, Alison A Motsinger-Reif

Determining the genes responsible for certain human traits can be challenging when the underlying genetic model takes a complicated form such as heterogeneity (in which different genetic models can result in the same trait) or epistasis (in which genes interact with other genes and the environment). Multifactor Dimensionality Reduction (MDR) is a widely used method that effectively detects epistasis; however, it does not perform well in the presence of heterogeneity partly due to its reliance on cross-validation for internal model validation. Cross-validation allows for only one "best" model and is therefore inadequate when more than one model could cause the same trait. We hypothesize that another internal model validation method known as a three-way split will be better at detecting heterogeneity models.