Modified entropy-based procedure detects gene-gene-interactions in unconventional genetic models

Background: Since it is assumed that genetic interactions play an important role in understanding the mechanisms of complex diseases, different statistical approaches have been suggested in recent years for this task. One interesting approach is the entropy-based IGENT method by Kwon et al. that promises an efficient detection of main effects and interaction effects simultaneously. However, a modification is required if the aim is to only detect interaction effects. Methods: Based on the IGENT method, we present a modification that leads to a conditional mutual information based approach under the condition of linkage equilibrium. The modified estimator is investigated in a comprehensive simulation based on five genetic interaction models and applied to real data from the genome-wide association study by the North American Rheumatoid Arthritis Consortium (NARAC). Results: The presented modification of IGENT controls the type I error in all simulated constellations. Furthermore, it provides high power for detecting pure interactions specifically on unconventional genetic models both in simulation and real data. Conclusions: The proposed method uses the IGENT software, which is free available, simple and fast, and detects pure interactions on unconventional genetic models. Our results demonstrate that this modification is an attractive complement to established analysis methods.