Genetic studies of complex human diseases: characterizing SNP-disease associations using Bayesian networks

Detecting epistatic interactions plays a significant role in improving pathogenesis, prevention, diagnosis, and treatment of complex human diseases. Applying machine learning or statistical methods to epistatic interaction detection will encounter some common problems, e.g., very limited number of samples, an extremely high search space, a large number of false positives, and ways to measure the association between disease markers and the phenotype.

To address the problems of computational methods in epistatic interaction detection, we propose a score-based Bayesian network structure learning method, EpiBN, to detect epistatic interactions. We apply the proposed method to both simulated datasets and three real disease datasets. Experimental results on simulation data show that our method outperforms some other commonly-used methods in terms of power and sample-efficiency, and is especially suitable for detecting epistatic interactions with weak or no marginal effects. Furthermore, our method is scalable to real disease data.

We propose a Bayesian network-based method, EpiBN, to detect epistatic interactions. In EpiBN, we develop a new scoring function, which can reflect higher-order epistatic interactions by estimating the model complexity from data, and apply a fast Branch-and-Bound algorithm to learn the structure of a two-layer Bayesian network containing only one target node. To make our method scalable to real data, we propose the use of a Markov chain Monte Carlo (MCMC) method to perform the screening process. Applications of the proposed method to some real GWAS (genome-wide association studies) datasets may provide helpful insights into understanding the genetic basis of Age-related Macular Degeneration, late-onset Alzheimer's disease, and autism.