A positive genetic correlation was found between genetic risk factors for cannabis use and schizophrenia (rg=0.24, SE=0.03, p<0.01). To examine whether there was evidence for a causal effect of cannabis use on schizophrenia risk and vice versa we performed bi-directional two-sample Mendelian randomization (MR) analysis22. In our main analysis (Inverse Variance Weighted [IVW] regression analysis) we found some weak (non-significant) evidence for a causal influence of lifetime cannabis use on schizophrenia risk, but only for the genetic instrument containing SNPs associated with cannabis use under the p-value threshold 1e-05. The IVW regression odds ratio was 1.10 (95% confidence intervals [CIs] 0.99-1.21, p=0.074). We found stronger evidence for a causal positive influence of schizophrenia risk on lifetime cannabis use, the IVW regression odds ratio being 1.16 (95% CIs 1.06-1.27, p=0.001; see Table 3, Supplementary Table S7-S9, and Supplementary Figure S9-S10 for details).
