Substantiating the idea that it is biologically plausible that reduced GMV in the DLPFC represents a preexisting genetic liability for drinking, genomic risk for alcohol use was enriched only within brain gene sets. BA 9, which overlaps with the DLPFC regions identified in our neuroimaging analyses, was among the regions of strongest enrichment (Figure 4). Further, TWAS analyses revealed replicable evidence that genomic risk for alcohol use is associated with differential expression of CWF19L1 and C18orf8 within BA 9. While the function of these genes is not understood, both have been previously implicated in psychopathology and related traits, including schizophrenia, substance use, and cognition (Supplement 1), with rare mutations in CWF19L1 causing autosomal recessive cerebellar ataxia (66,67), which is characterized by a loss of control of bodily movements, as well as developmental delay and mental retardation. Additional discussion of these findings and their limitations is presented in Supplement 1.
