FORGE: A tool to discover cell specific enrichments of GWAS associated SNPs in regulatory regions

Abstract

Genome Wide Association Studies (GWAS) provide an unbiased discovery mechanism for numerous human diseases. However, a frustration in the analysis of GWAS is that the majority of variants discovered do not directly alter protein-coding genes. We have developed a simple analysis approach that detects the tissue-specific regulatory component of a set of GWAS SNPs by identifying enrichment of overlap with DNase I hotspots from diverse tissue samples. Functional element Overlap analysis of the Results of GWAS Experiments (FORGE) is available as a web tool and as standalone software and provides tabular and graphical summaries of the enrichments.  Conducting FORGE analysis on SNP sets for 260 phenotypes available from the GWAS catalogue reveals numerous overlap enrichments with tissue-specific components reflecting the known aetiology of the phenotypes as well as revealing other unforeseen tissue involvements that may lead to mechanistic insights for disease.