Our findings should be interpreted in the context of at least four potential limitations. First, our study was underpowered to detect very small effects of individual variants. Power analyses revealed that a twofold increase in sample size is required to detect SNP effect sizes with odds ratios of 1.1. Second, lifetime cannabis use is a dichotomous measure combining single lifetime, regular and chronic users. Consequently, our sample may compromise heterogeneous patterns of use, which has the potential to reduce the power to detect genetic association.68 Third, prevalences of lifetime cannabis use varied between 1% (EGCUT1) and 92% (Yale Penn EA). This was likely due to differences in the sample characteristics, recruitment strategies and the political differences between countries. Despite these differences, the forest plots of the key SNPs (see Figure 2; see also Supplementary Figure 5) revealed that the 95% confidence intervals surrounding the effect estimates typically included the estimated meta-analytic effect, which tends to overlap across studies. This indicates that the input samples were representative of the same population of users. Finally, the average age of participants varied between
