MRSamePopTest

MRSamePopTest implements a falsification test for the 'same population' assumption in two-sample Mendelian randomisation (2SMR) studies by testing the homogeneity of SNP effects for a shared phenotype across two populations.

Key Features:

• Falsification test for same-population assumption: Tests whether variant-phenotype associations for a phenotype measured in both genetic association studies are homogeneous across the two populations.
• Sensitivity analysis for population exchangeability: Evaluates whether effect modifiers are exchangeable between exposure and outcome GWAS populations based on recent theoretical developments in causal inference.
• R package implementation: Provides a simple, easy-to-implement computational framework for the proposed test.

Scientific Applications:

• Two-sample Mendelian randomisation validation: Validates the critical 'same population' assumption required for interpretable 2SMR point estimates when exposure and outcome GWASs are derived from different samples.
• MR study design with diverse populations: Facilitates the design of Mendelian randomisation studies that incorporate genetically diverse populations by enabling formal assessment of population comparability.
• Complement to demographic similarity checks: Provides a genetic-level sensitivity analysis to augment standard demographic comparisons of genetic association studies.

Methodology:

The test assesses homogeneity of variant-phenotype associations for a phenotype measured in both genetic association studies, based on the principle that causal effect estimates generalise between studies if there is exchangeability of effect modifiers.