Pair-Wise Multifactor Dimensionality Reduction Method to Detect Gene-Gene Interactions in A Case-Control Study

The identification of gene-gene interactions has been limited by small sample size and large number of potential interactions between genes. To address this issue, Ritchie et al. [2001] have proposed multifactor dimensionality reduction (MDR) method to detect polymorphisms associated with the disease risk. The MDR reduces the dimension of the genetic factors by classifying them into high-risk and low-risk groups. The strong point in favor of MDR is that it can detect interactions in absence of significant main effects. However, it often suffers from the sparseness of the cells in high-dimensional contingency tables, since it cannot classify an empty cell as high risk or low risk.