We report convergent evidence that smaller GMVs of the right insula and DLPFC (i.e., middle and superior frontal gyri) plausibly represent genetically conferred liabilities that promote early alcohol use. First, we show that smaller GMVs of the right insula and DLPFC were replicably associated with alcohol use in 2 large neuroimaging samples. Second, family-based data provide evidence that these associations are attributable to shared genetic factors with no evidence of a causal association, or that shared or unique environmental factors contribute to this association. Third, reduced DLPFC volume prospectively predicted future alcohol use among young adults as well as alcohol use initiation during adolescence among children and adolescents who were unexposed to alcohol at baseline. Finally, we found evidence that genomic risk for alcohol use is enriched among genes that are preferentially expressed within the DLPFC and is replicably predictive of gene expression in the DLPFC. Collectively, these convergent data suggest that lower GMVs in the middle and superior frontal gyri and insula may represent a preexisting genetic liability for drinking that could serve as a prognostic biomarker. Further, these
