Gene-based association and partitioned heritability enrichment analyses of the UK Biobank GWAS of alcohol consumption revealed enrichment only among brain gene sets (Figure 4). Moreover, BA 9, which overlaps with the frontal region identified in neuroimaging analyses, was among the regions with strongest enrichment (Figure S4 in Supplement 1, Supplemental Data). A TWAS analysis of these GWAS data similarly found that genetic risk for alcohol consumption was significantly associated with differences in gene expression across the brain within the GTEx dataset, including expression of C16orf93 within BA 9 (Figure 5, Table 2, Supplemental Data). C16orf93 was not available in the TWAS replication dataset [i.e., the dataset of Schumann et al. (29) and the CommonMind Consortium (31)] (Table 2). Three additional genes survived FDR correction in BA 9, two of which (i.e., CWF19L1 and C18orf8) were available in the TWAS replication dataset (Figure 5, Table 2)1. Genomic risk for alcohol consumption was significantly predictive of differential expression of CWF19L1 and C18orf8 within the DLPFC of our TWAS replication dataset, in the same direction as was observed in the discovery dataset (Table
