FORGE

FORGE identifies tissue-specific regulatory overlap between Genome-Wide Association Study (GWAS) single nucleotide polymorphisms (SNPs) and DNase I hypersensitive sites to reveal functional non-coding variants and their tissue contexts.

Key Features:

• Tissue-Specific Regulatory Analysis: Identifies enrichment of overlap between GWAS SNPs and DNase I hypersensitive sites across tissue samples to pinpoint regulatory elements influenced by non-coding variants.
• DNase I Hypersensitivity Mapping: Uses DNase I hypersensitive sites as indicators of open chromatin to map SNP overlaps to putative regulatory regions.
• GWAS Catalogue Integration: Analyzes SNP sets from 260 phenotypes available in the GWAS catalogue to assess tissue-specific enrichment across diverse traits.
• Tabular and Graphical Summaries: Produces detailed tabular and graphical summaries of SNP enrichment results across tissues.
• Unbiased GWAS-Based Discovery: Leverages the unbiased sampling of GWAS results to explore tissue associations across a wide array of human diseases.

Scientific Applications:

• Annotation of GWAS Loci: Assigns tissue-specific regulatory context to GWAS SNPs and other non-coding variants.
• Interpretation of Non-Coding Variant Function: Reveals candidate regulatory mechanisms underlying trait-associated SNPs.
• Prioritization for Functional Follow-Up: Prioritizes tissues and regulatory elements for experimental validation based on enrichment patterns.
• Investigation of Disease Etiology: Provides insights into tissue-specific contributions to complex traits and diseases.
• Identification of Candidate Therapeutic Targets: Highlights regulatory elements associated with disease-linked SNPs that may inform therapeutic investigation.

Methodology:

Compute enrichment of overlap between GWAS SNPs and DNase I hypersensitive sites across tissue samples using SNP sets from 260 phenotypes in the GWAS catalogue and output results as tabular and graphical summaries.