psychiatric disorders) and 48,985 individuals not diagnosed with CUD, all from the iPSYCH cohort. We identify a genome-wide significant risk locus on chromosome 8, which replicates in an independt cohort from deCODE genetics. The index variant is a strong eQTL for CHRNA2, which encodes the neuronal acetylcholine receptor (nAChR) alpha-2 subunit, and in analyses of the genetically regulated gene expression we find reduced expression of CHRNA2 in brain tissue in individuals with CUD compared to the control group in cerebellum. At the polygenic level, we show that increased load of CUD variants associates with decreased cognitive performance and increased risk of schizophrenia and ADHD.
