Gene-Gene Interaction Analysis for the Survival Phenotype Based on the Kaplan-Meier Median Estimate

Abstract

In this study, we propose a simple and computationally efficient method based on the multifactor dimensional reduction algorithm to identify gene-gene interactions associated with the survival phenotype. The proposed method, referred to as KM-MDR, uses the Kaplan-Meier median survival time as a classifier. The KM-MDR method classifies multilocus genotypes into a binary attribute for high- or low-risk groups using median survival time and replaces balanced accuracy with log-rank test statistics as a score to determine the best model. Through intensive simulation studies, we compared the power of KM-MDR with that of Surv-MDR, Cox-MDR, and AFT-MDR. It was found that KM-MDR has a similar power to that of Surv-MDR, with less computing time, and has comparable power to that of Cox-MDR and AFT-MDR, even when there is a covariate effect. Furthermore, we apply KM-MDR to a real dataset of ovarian cancer patients from The Cancer Genome Atlas (TCGA).