Pleiotropic effects refer to the phenomenon in which a genetic variant affects multiple phenotypes (Solovieff et al., 2013).
It is critical to distinguish horizontal and vertical pleiotropy in MR analysis:
- Horizontal pleiotropy: the genetic variants affect the outcome through another trait or pathway to the one under study. This is problematic for MR studies because the effects of the genetic variant on the outcome are not exclusively through the risk factor, which violates the IV2 assumption.
- Vertical pleiotropy: the genetic variants affect the outcome through the risk factor of interest, which is the core of MR.