POEMColoc

POEMColoc estimates colocalization probabilities between genetic variants and phenotypes using complete or limited summary statistics to evaluate whether the same causal variant underlies GWAS and eQTL signals.

Key Features:

• Approximation of coloc: Implements an approximation of the coloc method to assess shared causality when full summary statistics are not available for both traits.
• Imputation using LD from a reference panel: Imputes missing summary statistics by leveraging linkage disequilibrium (LD) structure from a reference panel.
• Support for single top SNP data: Operates with datasets that contain either full summary statistics or only the single reported top SNP for a trait.
• Application to GWAS and eQTL data: Designed to test GWAS Catalog hits against GTEx expression quantitative trait loci (eQTL) data for colocalization analysis.
• Simulation-based validation: Performance has been evaluated via simulations showing comparable ability to identify shared causality to the coloc method.
• Factors affecting accuracy: Accuracy is influenced by multiple independent causal variants in a region, imputation from a limited subset of typed variants, and modestly by mismatched ancestry in the reference panel.

Scientific Applications:

• Colocalization of GWAS Catalog and GTEx eQTLs: Estimating colocalization between GWAS Catalog entries and GTEx eQTLs to link trait-associated loci to gene expression.
• Understanding genetic mechanisms: Determining whether the same variant affects multiple phenotypes to strengthen evidence for shared genetic mechanisms beyond shared significance.
• Prioritizing disease-relevant genes and drug targets: Identifying trait–gene pairs enriched in disease-relevant tissues and associations relevant to approved drug target–indication pairs.

Methodology:

Accepts full summary statistics or only a single top SNP; imputes missing summary statistics using LD structure from a reference panel; performs colocalization analysis between imputed statistics and complete data for a second trait; validation performed by simulation comparisons to coloc.