Interaction-based Mendelian randomization with measured and unmeasured gene-by-covariate interactions.

ABSTRACT: Studies leveraging gene-environment (GxE) interactions within Mendelian randomization (MR) analyses have prompted the emergence of two similar methodologies: MR-GxE and MR-GENIUS. Such methods are attractive in allowing for pleiotropic bias to be corrected when using individual instruments. Specifically, MR-GxE requires an interaction to be explicitly identified, while MR-GENIUS does not. We critically examine the assumptions of MR-GxE and MR-GENIUS in the absence of a pre-defined covariate, and propose sensitivity analyses to evaluate their performance. Finally, we explore the effect of body mass index (BMI) upon systolic blood pressure (SBP) using data from the UK Biobank, finding evidence of a positive effect of BMI on SBP. We find both approaches share similar assumptions, though diffe

SUBMITTER: Spiller W 

PROVIDER: S-EPMC9365161 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature