Examining parental remission from alcohol use disorder as a moderator of genetic predispositions for offspring alcohol use behaviors

Background. We tested whether parental remission from alcohol use disorder (AUD) would attenuate associations between offspring polygenic predispositions and alcohol milestones from initiation to AUD. Methods. Participants were 2,971 individuals from the Collaborative Study on the Genetics of Alcoholism Prospective Sample. Outcomes included ages at initiation of regular drinking, first intoxication, first AUD criterion, and first AUD diagnosis. Parental AUD and remission were coded separately for mothers and fathers using four categories: unaffected, unremitted AUD, remitted AUD, and probable AUD/remission unknown. Offspring genetic predispositions were indexed using genome-wide polygenic scores for problematic alcohol use (PGSPAU). Mixed-effects Cox models were used.Results. In main effects models, having a remitted AUD mother or father was significantly associated with higher hazards of all alcohol outcomes compared to unaffected parents [HR range: 1.22-1.52], but did not differ significantly from parents with unremitted AUD. Higher PGSPAU was associated with increased hazards across outcomes. Interaction models provided limited evidence that parental remission moderated associations between PGSPAU and alcohol outcomes. The only interaction that remained significant after multiple testing correction indicated that the association between PGSPAU and AUD diagnosis was weaker among offspring with remitted AUD mothers than those with unaffected mothers (HRinteraction = 0.76, 95% CI = [0.65, 0.90], adj. p = 0.024).Conclusions. Hazards of all alcohol milestones were similar among offspring with remitted and unremitted parental AUD, with little evidence that parental remission buffered genetic liability. Genetic influences on AUD were attenuated among offspring of mothers in remission compared to those with AUD-unaffected mothers.