As interactions among genetic variants in different genes can be an important factor for predicting complex diseases, many computational methods have been proposed to detect if a particular set of genes has interaction with a particular complex disease. However, even though many such methods have been shown to be useful, they can be made more effective if the properties of gene-gene interactions can be better understood. Towards this goal, we have attempted to uncover patterns in gene-gene interactions and the patterns reveal an interesting property that can be reflected in an inequality that describes the relationship between two genotype variables and a disease-status variable. We show, in this paper, that this inequality can be generalized to [Formula: see text] genotype variables. Based on this inequality, we establish a conditional independence and redundancy (CIR)-based definition of gene-gene interaction and the concept of an interaction group. From these new definitions, a novel measure of gene-gene interaction is then derived. We discuss the properties of these concepts and explain how they can be used in a novel algorithm to detect high-order gene-gene interactions. Experimental results using both simulated and real datasets show that the proposed method can be very promising.
Keywords: Complex diseases; gene–gene interaction; interaction group; mutual information.