Using the global randomization test as a Mendelian randomization falsification test for the exclusion restriction assumption.

ABSTRACT: Mendelian randomization may give biased causal estimates if the instrument affects the outcome not solely via the exposure of interest (violating the exclusion restriction assumption). We demonstrate use of a global randomization test as a falsification test for the exclusion restriction assumption. Using simulations, we explored the statistical power of the randomization test to detect an association between a genetic instrument and a covariate set due to (a) selection bias or (b) horizontal pleiotropy, compared to three approaches examining associations with individual covariates: (i) Bonferroni correction for the number of covariates, (ii) correction for the effective number of independent covariates, and (iii) an r² permutation-based approach. We conducted proof-of-principle

SUBMITTER: Millard LAC 

PROVIDER: S-EPMC11410989 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature