<p>Extensive research has documented altered emotion processing in binge drinkers. Genetic risks contribute to problem drinking; however, it remains unclear how genetic risks for alcohol misuse affect behavioral and brain responses to negative emotions. We curated data from the Human Connectome Project and identified 97 binge (69 men) and 379 demographically-matched non-binge (142 men) drinkers performing an emotion task during brain imaging. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures. Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects. With published routines and at a corrected threshold, we evaluated how brain responses to matching negative emotional faces vs. geometric shapes associated with PC1 and PRS in a linear regression, with age, sex, and race as covariates. Higher PC1 and PRS were both significantly correlated with greater symptom severity of somatic complaints in binge drinkers. Bingers relative to non-bingers showed stronger activation of a wide array of frontal, parietal and occipital regions and the insula in positive correlation with the PRS. These genetic risk markers featured more prominently in male than in female binge drinkers. In contrast, regional responses in the default mode network may represent sex-shared markers of the genetic risks. These findings suggest altered neurobiological processes of negative emotions in correlation with genetic risks for alcohol misuse in binge drinkers. Longitudinal studies are needed to show how dysfunctional negative emotion processing interlinks the genetic risks and problem drinking.</p>