Smaller right dorsolateral prefrontal cortex (DLPFC; i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest these associations are genetically-conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene-sets preferentially expressed in the DLPFC, and associated with replicable differential gene expression in the DLPFC.
These data suggest that smaller DLPFC and insula GMV plausibly represent genetically-conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol consumption liability and related psychiatric and behavioral phenotypes.