This is the first study to demonstrate the influence of polygenic risk for alcohol dependence on EEG coherence, an important marker of cognitive functioning and AUD, alongside neuropsychological performance, and lifetime alcohol and opioid use disorders. Findings from this study demonstrate clear differences among males and females in the association of polygenic risk for alcohol dependence and neural connectivity across adolescent and young adult development. These findings also suggest that patterns of polygenic association with neural connectivity differ with respect to age among those with and without lifetime AUD. Results from this study show that connectivity differences associated with PRS predate significant alcohol use, suggesting that the EEG coherence is likely a marker of risk, rather than a consequence of heavy alcohol use. Therefore, the cognitive deficits reflected by EEG coherence levels and neuropsychological performance may be one mechanism by which polygenic risk increases risk for AUD. While polygenic risk scores for AUD have yet to reach the point of clinical utility (i.e., family history of AUD remains a stronger predictor than any PRS), larger and more diverse GWAS of
