Searching Genome-Wide Multi-Locus Associations for Multiple Diseases Based on Bayesian Inference.

Abstract

Taking the advantage of high-throughput single nucleotide polymorphism (SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unraveling complex relationships between genotypes and phenotypes. Current multi-locus-based methods are insufficient to detect interactions with diverse genetic effects on multifarious diseases. Also, statistic tests for high-order epistasis ( ≥ 2 SNPs) raise huge computational and analytical challenges because the computation increases exponentially as the growth of the cardinality of SNPs combinations. In this paper, we provide a simple, fast and powerful method, named DAM, using Bayesian inference to detect genome-wide multi-locus epistatic interactions in multiple diseases. Experimental results on simulated data demonstrate that our method is powerful and efficient. We also apply DAM on two GWAS datasets from WTCCC, i.e., Rheumatoid Arthritis and Type 1 Diabetes, and identify some novel findings. Therefore, we believe that our method is suitable and efficient for the full-scale analysis of multi-disease-related interactions in GWASs.