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Emily A King1, Fengjiao Dunbar1, Justin Wade Davis1

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Summary

A new method, POEMColoc, approximates colocalization analysis using limited genetic summary statistics. This enables large-scale genetic studies by imputing missing data, revealing 150,000 trait-gene-tissue links.

Keywords:
ColocalizationExpression quantitative trait locusGTExGWASGWAS catalogGenome-wide association studyeQTL

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Area of Science:

  • Genetics
  • Statistical Genetics
  • Bioinformatics

Background:

  • Colocalization is a statistical genetics method to identify shared causal variants across multiple phenotypes.
  • Existing colocalization methods require full summary statistics, limiting their application to large genetic association databases.
  • This limitation hinders the analysis of the majority of reported Genome-Wide Association Studies (GWAS) associations.

Purpose of the Study:

  • To develop a novel approximation method for colocalization analysis when only limited summary statistics are available.
  • To enable colocalization analysis using readily available GWAS data, such as from the GWAS Catalog.
  • To expand the scope of genetic colocalization studies to a larger number of traits and genes.

Main Methods:

  • Proposed a new method, POint EstiMation of Colocalization (POEMColoc), which approximates the popular coloc method.
  • POEMColoc imputes missing summary statistics using linkage disequilibrium (LD) structure from a reference panel.
  • The method performs colocalization analysis using these imputed summary statistics, allowing for analysis with limited data.

Main Results:

  • POEMColoc demonstrated good correlation between posterior probabilities of colocalization from imputed and observed datasets.
  • The method showed similar accuracy in simulations, with performance affected by multiple independent causal variants and limited typed variants.
  • Application to GWAS Catalog and GTEx eQTL data identified 150,000 trait-gene-tissue triplets with evidence of colocalization.

Conclusions:

  • Colocalization analysis can be accurately approximated using only top SNP summary statistics when full data is unavailable.
  • POEMColoc successfully identified numerous colocalized trait-gene pairs, enriched in disease-relevant tissues and drug mechanisms.
  • The POEMColoc R package is publicly available for broader use in genetic research.