To further evaluate the potential regulatory impact of the identified locus on chromosome 8 as well as genome-wide gene expression differences between cases and controls, we imputed the genetically regulated gene expression in 11 brain tissues using PrediXcan (Methods). The SNP weights used were derived from models trained on reference transcriptome data sets including 10 brain tissues from GTEx and transcriptome data from dorsolateral prefrontal cortex generated by the CommonMind Consortium.. We tested for association of expression of 2,460-10,930 protein coding genes depending on the tissue (Supplementary Table 6) with CUD using logistic regression corrected by the same covariates as in the GWAS. One gene, CHRNA2, was significantly differently expressed between cases and controls (P=2.713x10−6; beta=−0.21; SE=0.045) in the cerebellum. The expression model for CHRNA2 in cerebellum was based on 47 SNPs including four genome-wide significant SNPs rs59724122, rs73229093, rs7838316 and rs11783093 (Figure 3). CHRNA2 expression was predicted with a valid model in two other brain tissues showing nominal significant under-expression in cases compared to controls (dorsolateral prefrontal cortex, P=5.19x10−4; cerebellar hemisphere P=5.30x10−3). That the risk locus for CUD can
