Given evidence that genetic liability is shared across substance use involvement (67) and other forms of psychopathology (68), our findings may generalize to other substances and overall psychopathology risk. While enrichment analyses implicate only brain pathways and TWASs identify replicable associations between genetic risk for alcohol consumption and gene expression in the frontal cortex, we cannot rule out the possibility that our observed effects are partially mediated by altered functioning of other pathways, such as alcohol metabolism in the liver (69). Moreover, the present results do not distinguish between reduced GMV as part of the mechanism by which genetic risk affects drinking behavior (10,70) and a pleiotropic effect of genetic risk on multiple outcomes (20).
