Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with 'cigarette smoking initiation' really capturing?

ABSTRACT: Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results. We examined the extent of this using smoking behaviours as an example. We first ran a phenome-wide association study in UK Biobank, using a smoking initiation genetic instrument. From the most strongly associated phenotypes, we selected those we considered could either plausibly or not plausibly be caused by smoking. We examined associations between genetic instruments for smoking initiation, smoking heaviness and lifetime smoking and these phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). We conducted n

SUBMITTER: Reed ZE 

PROVIDER: S-EPMC7616876 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature