Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization.

ABSTRACT: With the increasing size and number of genome-wide association studies, individual single nucleotide polymorphisms are increasingly found to associate with multiple traits. Many different mechanisms could result in proposed genetic IVs for an exposure of interest being associated with multiple non-exposure traits, some of which could bias MR results. We describe and illustrate, through causal diagrams, a range of scenarios that could result in proposed IVs being related to non-exposure traits in MR studies. These associations could occur due to five scenarios: (i) confounding, (ii) vertical pleiotropy, (iii) horizontal pleiotropy, (iv) reverse causation and (v) selection bias. For each of these scenarios we outline steps that could be taken to explore the underlying mechanism and mitigate

SUBMITTER: Yang Q 

PROVIDER: S-EPMC9329407 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature