The signal observed for the index variant in the GWAS meta-analysis of schizophrenia19 (rs73229090) is consistent with the direction of association observed in our analysis. Since individuals with schizophrenia often use cannabis (around 13-16%22) it could be speculated that the significant signal observed in schizophrenia is driven by a sub-group of schizophrenia cases also having CUD. This hypothesis is supported by analysis of the association of rs56372821 with schizophrenia in the iPSYCH sample. We found a nominal significant association of the variant with schizophrenia when including individulas with co-morbid CUD (2,281 schizophrenia cases and 23,134 controls; OR=0.9; P=0.036), while after exclusion of individuals with CUD (556 cases and 101 controls excluded) the association signal disappeared (1,727 cases, 23,033 controls; OR=0.97, P=0.63). To further to evaluate the impact of CUD comorbidity on the odds ratio of rs56372821 in schizophrenia a null distribution for the odds ratio was generated by performing 10,000 permutations randomly removing 556 and 101 individuals among the cases and controls, respectively (Supplementary Figure 1). The observed odds ratio for rs56372821, when excluding individuals with comorbid CUD was 0.97,
