The risk locus on chromosome 8 is also genome-wide significantly associated with schizophrenia19. In our leave-one-phenotype out analysis the locus remained genome-wide significant when individuals with schizophrenia were removed, excluding any potential confounding from schizophrenia (Table 2). Additionally, we tested the possibility of the locus being broadly associated with psychiatric disorders by performing a cross disorder GWAS including 35,006 individuals with one of the five major psychiatric disorders and 16,366 controls. In this analysis the index variant (rs56372821) showed a P-value of 0.058 (OR=0.966). When redoing the GWAS while excluding all individuals with CUD, the analysis revealed a cross-disorder P-value=0.33, OR=0.982 for rs56372821 (32,716 cases and 16,269 controls). The close to nominal significant signal observed in the cross-disorder GWAS including all cases disappeared when excluding individuals having a CUD diagnosis. This reinforces that the association signal in the CUD GWAS is caused by CUD, and not by a general association with psychiatric disorders.
