GWAS-GMDR: A program package for genome-wide scan of gene-gene interactions with covariate adjustment based on multifactor dimensionality reduction

Multifactor dimensionality reduction (MDR) has been successfully applied to identification of gene-gene interactions for the complex traits. Generalized MDR (GMDR) was its extension that allows adjustment for covariates. The current GMDR software mainly focuses on candidate gene association studies with a relatively small number of genetic markers and has some limitations to be extended to genome-wide association studies (GWAS) with a large number of genetic markers. We develop GWAS-GMDR, an effective parallel computing program package with special features for GWAS with a large number of genetic markers by using distributed job scheduling method and/or CUDA-enabled high-performance graphic processing units (GPU). First, GWAS-GMDR implements an effective memory handling algorithm and efficient procedures for GMDR to make joint analysis of multiple genes feasible for GWAS. Second, a weighted version of cross-validation consistency based on `top-K selection´ (WCVC^K) is proposed to report multiple candidates for causal gene-gene interactions. Third, various performance measures are implemented to evaluate MDR classifiers, including balanced accuracy, tau-b, likelihood ratio and normalized mutual information. Fourth, some popular methods for handling missing genotypes are implemented. Finally, our applications support both CPU-based and GPU-based parallel computing system. We applied our applications using a real genome wide data set from WTCCC Crohn´s disease dataset to identify two-way interaction models in genome-wide scale. The GWAS-GMDR package is a powerful tool for the gene-gene interaction analysis in a genome-wide scale. High-performance implementations are provided as native binaries for Linux, Mac OS X and Windows systems.