Fig. 2

Graphical representation of the Mendelian randomization approach. The risk estimate for the gene-schizophrenia association of the T allele of the MTHFR C677T polymorphism was obtained from the present meta-analysis of previous genetic association studies that cover a total of 25,599 individuals (11,042 cases and 14,557 controls). To establish the gene-homocysteine association, we took a pooled estimate of the effect of the MTHFR C677T polymorphism on the plasma total homocysteine levels from a recent meta-analysis of previous genome-wide association studies, including 44,147 individuals (van Meurs et al. [2]). From these two estimates, we calculated a Mendelian randomization estimate of the effect of the plasma total homocysteine levels on the risk of schizophrenia. This estimate represented the OR for schizophrenia risk per 1-SD increase in the log-transformed plasma total homocysteine levels