Incorporating biological and clinical insights into variant choice for Mendelian randomisation: examples and principles.

ABSTRACT: Mendelian randomisation is an accessible and valuable epidemiological approach to provide insight into the causal nature of relationships between risk factor exposures and disease outcomes. However, if performed without critical thought, we may simply have replaced one set of implausible assumptions (no unmeasured confounding or reverse causation) with another set of implausible assumptions (no pleiotropy or other instrument invalidity). The most critical decision to avoid pleiotropy is which genetic variants to use as instrumental variables. Two broad strategies for instrument selection are a biologically motivated strategy and a genome-wide strategy; in general, a biologically motivated strategy is preferred. In this review, we discuss various ways of implementing a biologically motivate

SUBMITTER: Burgess S 

PROVIDER: S-EPMC7615644 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature