Fig. 1

The conceptual framework of Mendelian Randomization. Mendelian randomization study uses genetic information (SNPs, instruments, IVs) as proxy for exposure to understand a causal inference between an exposure and an outcome. An un-confounded causal estimation can be made based on the observed IV-exposure and IV-outcome associations under certain assumptions. Namely, the selected IVs are associated with the exposure (red solid arrow), but not associated with any confounder of the exposure-outcome relationship (gray dash arrow), nor associated with the outcome via pathways other than through the exposure (gray dash arrow)