Robust Mendelian randomization in the presence of residual population stratification, batch effects and horizontal pleiotropy.

ABSTRACT: Mendelian Randomization (MR) studies are threatened by population stratification, batch effects, and horizontal pleiotropy. Although a variety of methods have been proposed to mitigate those problems, residual biases may still remain, leading to highly statistically significant false positives in large databases. Here we describe a suite of sensitivity analysis tools that enables investigators to quantify the robustness of their findings against such validity threats. Specifically, we propose the routine reporting of sensitivity statistics that reveal the minimal strength of violations necessary to explain away the MR results. We further provide intuitive displays of the robustness of the MR estimate to any degree of violation, and formal bounds on the worst-case bias caused by violations

SUBMITTER: Cinelli C 

PROVIDER: S-EPMC8888767 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature