POIROT

POIROT detects parent-of-origin effects (POEs) in unrelated samples by comparing phenotypic covariance matrices of heterozygotes and homozygotes with a Robust Omnibus Test to leverage pleiotropy across multiple correlated quantitative traits in GWAS.

Key Features:

• Pleiotropy Utilization: Analyzes multiple correlated quantitative traits simultaneously to increase power for detecting POEs compared with univariate methods.
• Robustness: Employs a Robust Omnibus Test that is calibrated against non-normality and accounts for population stratification and other potential confounders.
• Simulation Validation: Demonstrated greater power and accuracy than univariate variance-based methods in simulation studies.

Scientific Applications:

• Large-scale GWAS: Enables detection of POEs in unrelated individuals to study the genetic architecture of complex traits using multi-phenotype analyses.
• UK Biobank analysis: Applied to UK Biobank BMI and cholesterol phenotypes to identify 338 genome-wide significant loci for follow-up.

Methodology:

The method compares covariance matrices between heterozygotes and homozygotes across multiple quantitative traits using a Robust Omnibus Test.