Genetic Risk for Trait Aggression and Alcohol Use Predict Unique Facets of Alcohol-Related Aggression

Objective: A propensity for aggression or alcohol use may be associated with alcohol-related aggression. Previous research has shown genetic overlap between alcohol use and aggression but has not looked at how alcohol-related aggression may be uniquely influenced by genetic risk for aggression or alcohol use. The present study examined the associations of genetic risk for trait aggression, alcohol use, and alcohol use disorder (AUD) with alcohol-related aggression using a polygenic risk score (PRS) approach. Method: Using genome-wide association study summary statistics, PRSs were created for trait aggression, alcohol consumption, and AUD. These PRSs were used to predict the phenotype of alcohol-related aggression among drinkers in two independent samples: the University of California at San Francisco (UCSF) Family Alcoholism Study (n = 1,162) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,291). Results: There were significant associations between the AUD PRS and lifetime alcohol-related aggression in the UCSF study sample. Additionally, the trait aggression PRS was associated with three or more experiences of hitting anyone else and getting into physical fights while under the influence of alcohol, along with a composite score of three or more experiences of alcohol-related aggression, in the UCSF study sample. No significant associations were observed in the Add Health sample. Limited sex-specific genetic effects were observed. Conclusions: These results provide preliminary evidence that genetic influences underlying alcohol use and aggression are uniquely associated with alcohol-related aggression and suggest that these associations may differ by type and frequency of alcohol-related aggression incidents. Public Health Significance Statement The findings in this report provide evidence for the multifaceted etiology of alcohol-related aggression and suggest that treatment goals related to alcohol-related aggression should target both alcohol use disorder and underlying trait aggression.