Interactive effects of genetic liability and combat exposure on risk of alcohol use disorder among US service members

Background: An improved understanding of pathways to alcohol use disorder (AUD) among service members may inform efforts to reduce the substantial impact of AUD on this population. This study examined whether the relationship between a service-related risk factor (combat exposure) and later AUD varied based on individual differences in genetic liability to AUD. Methods: The sample consisted of 1203 US Army soldiers of genetically determined European ancestry who provided survey and genomic data in the Army STARRS Pre/Post Deployment Study (PPDS; 2012–2014) and follow-up survey data in wave 1 of the STARRS Longitudinal Study (2016–2018). Logistic regression was used to estimate the conditional effect of combat exposure level (self-reported in PPDS) on odds of probable AUD diagnosis at follow-up, as a function of a soldier's polygenic risk score (PRS) for AUD. Results: The direct effect of combat exposure on AUD risk was non-significant (AOR=1.12, 95 % CI=1.00–1.26, p=.051); however, a significant combat exposure x PRS interaction was observed (AOR=1.60, 95 % CI=1.03–2.46, p=.033). Higher combat exposure was more strongly associated with elevated AUD risk among soldiers with heightened genetic liability to AUD. Conclusions: The effect of combat exposure on AUD risk appeared to vary based on a service member's level of genetic risk for AUD. Continued investigation is warranted to determine whether PRS can help stratify AUD risk within stress-exposed groups such as combat-deployed soldiers. Such efforts might reveal opportunities to focus prevention efforts on smaller subgroups at the intersection of having both environmental exposures and genetic vulnerability to AUD.