Fig. 1

Diagram for Mendelian randomization (MR). MR was developed on the premise of three assumptions. First, SNPs designated as instrumental variables (IVs) should be significantly associated with the exposure (Assumption 1). Second, SNPs selected as IVs are required to be independent of confounders (Assumption 2). Third, rather than being directly correlated, the relationship between IVs and the risk of SCZ (outcome) only occurs vis-a-vis reproductive variables (exposure) (Assumption 3). Fourth, the first assumption in the MVMR (Assumption 4) is that genetic variations are caused by one or more of the exposures. BMI, body mass index; YS, years of schooling; PA, physical activity; SI, smoking initiation; AD, alcoholic drinks per week; CI, coffee intake