A Scoring System to Evaluate the Impact of SNPs in a Path Related Context to Study Behçet’s Disease Aetiology in Japanese Population

Motivation Genome-wide association study (GWAS) is a powerful method that can provide a list of single nucleotide polymorphisms (SNPs) that are significantly related to the pathogenesis of a disease. Even though in Mendelian diseases strong associations can be found for certain SNPs, in most of the complex diseases only modest associations can be identified from the GWAS. Therefore, the main challenge in such studies is to understand how multiple SNPs that have modest association with the phenotype interact and contribute to its aetiology. This can only be done via pathway based analysis of modestly associated SNPs and the genes that are affected by these changes. Results In this study, we propose DAPath, a Disease Associated Path analyzer tool for discovering signaling paths and the pathways that contain these paths which are subjected to cumulative impact of modestly associated variants. We applied our proposed method on Behçet’s disease (BD) GWAS dataset from Japanese population. Antigen Processing and Presentation pathway is ranked first with 16 highly affected paths. Th17 cell differentiation, Natural killer cell mediated cytotoxicity, Jak-STAT signaling, and Circadian rhythm pathways are also found to be containing highly affected paths. Availability The proposed method is available as a Cytoscape plug-in through https://github.com/ozanozisik/DAPath