Association of parental divorce, discord, and polygenic risk with children's alcohol initiation and lifetime risk for alcohol use disorder

• Published in: Alcohol, clinical & experimental research clinical & experimental research, 2023-04, Vol.47 (4), p.724-735
• Main Authors: Kuo, Sally I‐Chun, Thomas, Nathaniel S., Aliev, Fazil, Bucholz, Kathleen K., Dick, Danielle M., McCutcheon, Vivia V., Meyers, Jacquelyn L., Chan, Grace, Kamarajan, Chella, Kramer, John R., Hesselbrock, Victor, Plawecki, Martin H., Porjesz, Bernice, Tischfield, Jay, Salvatore, Jessica E.
• Format: Article
• Language: English
• Subjects: Adult; Alcohol Drinking - adverse effects; Alcohol Drinking - epidemiology; Alcohol Drinking - genetics; Alcohol use; alcohol use disorder; Alcohol-Related Disorders; Alcoholism - epidemiology; Alcoholism - genetics; Child; Children; Children & youth; Divorce; Drinking behavior; Female; gene–environment; Humans; Male; Offspring; parental conflict; Parents; polygenic scores; Stress
• ISSN: 0145-6008; 2993-7175; 1530-0277; 2993-7175
• DOI: 10.1111/acer.15042

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, Mage ~ 36 years) and African (AA; N = 1714, 46% female, Mage ~ 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 risk scores (PRSALC). Mixed effects Cox proportional hazard models were used to examine alcohol initiation and generalized linear mixed effects models were used to examine 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 PRSALC 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. PRSALC was not associated with either. Parental divorce/discord and PRSALC 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. While many children exposed to common family stressors develop alcohol problems, not all do. The results from this study suggest that exposure to parental divorce/discord and children's genetic risk for alcohol problems jointly influence their risk for early alcohol initiation and developing alcohol use disorder, with some differences across European and African ancestry groups. Children who are exposed to parental divorce and discord and who also are genetically predisposed to alcohol problems are especially vulnerable to developing alcohol problems.