BACKGROUND: Parental divorce and discord are associated with poorer alcohol-related outcomes for offspring. However, not all children exposed to these stressors develop alcohol problems. Our objective was to test gene-by-environment interaction effects whereby children's genetic risk for alcohol problems modifies the effects of parental divorce and discord to predict alcohol outcomes.

METHODS: The sample included European (EA; N=5608, 47% male, M ~36 years) and African (AA; N=1714, 46% female, M ~ 33 years) ancestry participants from the Collaborative Study on the Genetics of Alcoholism. Outcomes included age at initiation of regular drinking and lifetime DSM-5 Alcohol Use Disorder (AUD). Predictors included parental divorce, parental relationship discord, and offspring alcohol problems polygenic scores (PRS ). Mixed effects Cox proportional hazard models were used for alcohol initiation, and generalized linear mixed effects models were used for lifetime AUD. Tests of PRS moderation of the effects of parental divorce/relationship discord on alcohol outcomes were examined on multiplicative and additive scales.

RESULTS: Among EA participants, parental divorce, parental discord, and higher PRS were associated with earlier alcohol initiation, and greater lifetime AUD risk. Among AA participants, parental divorce was associated with earlier alcohol initiation, and discord was associated with earlier initiation and AUD. PRS were not associated with either. Parental divorce/discord and PRS interacted on an additive scale in the EA sample, but no interactions were found in AA participants.

CONCLUSIONS: Children's genetic risk for alcohol problems modifies the impact of parental divorce/discord, consistent with an additive model of diathesis-stress interaction, with some differences across ancestry.