Multiple-Criteria Decision Analysis-Based Multifactor Dimensionality Reduction for Detecting Gene–Gene Interactions

Gene-gene interactions (GGIs) are important markers for determining susceptibility to a disease. Multifactor dimensionality reduction (MDR) is a popular algorithm for detecting GGIs and primarily adopts the correct classification rate (CCR) to assess the quality of a GGI. However, CCR measurement alone may not successfully detect certain GGIs because of potential model preferences and disease complexities. In this study, multiple-criteria decision analysis (MCDA) based on MDR was named MCDA-MDR and proposed for detecting GGIs. MCDA facilitates MDR to simultaneously adopt multiple measures within the two-way contingency table of MDR to assess GGIs; the CCR and rule utility measure were employed. Cross-validation consistency was adopted to determine the most favorable GGIs among the Pareto sets. Simulation studies were conducted to compare the detection success rates of the MDR-only-based measure and MCDA-MDR, revealing that MCDA-MDR had superior detection success rates. The Wellcome Trust Case Control Consortium dataset was analyzed using MCDA-MDR to detect GGIs associated with coronary artery disease, and MCDA-MDR successfully detected numerous significant GGIs (p <; 0.001). MCDA-MDR performance assessment revealed that the applied MCDA successfully enhanced the GGI detection success rate of the MDR-based method compared with MDR alone.