In summary, we identified a genome-wide significant CUD locus, which replicated in an independent sample. An impact of the locus on earlier age of first diagnosis was further suggested. CHRNA2 was implicated in CUD through analyses of the imputed genetically regulated gene expression, showing decreased CHRNA2 expression in cerebellum (and other brain regions) of individuals with CUD. An intriguing result, which suggests further studies to evaluate if CHRNA2 could be a pontential therapeutic target for CUD treatment. The identified locus is located in a region previously associated with schizophrenia19, smoking30 and lung cancer43. Our GWAS result with respect to the identified risk locus did not seem to be confounded by either smoking or psychiatric disorders. Larger GWASs and functional studies are needed in order to further explain the biological mechanisms underlying the phenotypic associations observed for this region.
