GREGOR

GREGOR assesses the enrichment of trait-associated genetic variants identified by GWAS within experimentally annotated epigenomic regulatory features to identify tissue- and cell-type–relevant regulatory elements and candidate functional variants.

Key Features:

• Statistical Rigor: Employs a statistically rigorous enrichment analysis to evaluate overlaps between genetic variants and regulatory features.
• Versatility in Data Analysis: Analyzes any set of genetic variants against any collection of experimentally annotated regulatory features.
• Data-Driven Approach: Uses a data-driven methodology to determine the most relevant tissues and cell types associated with a given trait.
• Identification of Functional Variants: Systematically evaluates enrichment across extensive regulatory datasets to pinpoint regulatory features and candidate functional variants at trait-associated loci.
• Experimental Validation: Predictions have been experimentally validated, including evaluation of six predicted functional variants at lipid-associated loci showing allele-specific impacts on expression levels.

Scientific Applications:

• Mechanistic interpretation of GWAS loci: Links trait-associated variants to regulatory elements that may modulate gene expression, supporting mechanistic interpretation of disease associations.
• Tissue and cell type prioritization: Identifies tissues and cell types most relevant to a trait by enrichment of variants in tissue-specific regulatory features.
• Prioritization of candidate functional variants: Guides identification of candidate functional variants at trait-associated loci for downstream functional follow-up.
• Functional genomics validation support: Provides candidate variants and regulatory features for experimental validation, as demonstrated at lipid-associated loci.

Methodology:

Performs statistically rigorous overlap and enrichment analyses between GWAS-derived trait-associated variants and experimentally annotated epigenomic regulatory features, using a data-driven approach to prioritize tissues and cell types.