A Critical Look at Entropy‐Based Gene‐Gene Interaction Measures

Several entropy‐based measures for detecting gene‐gene interaction have been proposed recently. It has been argued that the entropy‐based measures are preferred because entropy can better capture the nonlinear relationships between genotypes and traits, so they can be useful to detect gene‐gene interactions for complex diseases. These suggested measures look reasonable at intuitive level, but so far there has been no detailed characterization of the interactions captured by them. Here we study analytically the properties of some entropy‐based measures for detecting gene‐gene interactions in detail. The relationship between interactions captured by the entropy‐based measures and those of logistic regression models is clarified. In general we find that the entropy‐based measures can suffer from a lack of specificity in terms of target parameters, i.e., they can detect uninteresting signals as interactions. Numerical studies are carried out to confirm theoretical findings.