Polygenic Risk for Alcohol Misuse is Moderated by Romantic Partnerships: Primarily in Men

Importance: Problematic alcohol use remains a leading influence on preventable mortality and morbidity across the globe. Those in committed relationships consistently report lower levels of alcohol misuse and problems. Objective: To determine 1) whether genetic risk for alcohol misuse is moderated by romantic relationships (gene-environment interaction; GxE), and 2) whether GxE results are consistent across sex. Design: Data came from the young adult wave of the Finnish Twin Study (FinnTwin12), a nationally representative sample of twins. Predictors included genome-wide polygenic scores (GPS), derived from a recent genome-wide association study (GWAS) of alcohol consumption in ~1 million participants; and participant reports of relationship status. Setting: Finland. Participants: An intensively studied subset of FinnTwin12 received a diagnostic interview during the young adult phase (1,312 of 1,347 individuals provided genotypic data). The analytic sample includes those with complete interview and genetic data (N=1,201, 54% female). Exposure: Self-reported involvement in a romantic partnership. Main Outcomes and Measures: Drinking frequency, intoxication frequency, and DSM-IV alcohol dependence (AD) symptoms from a diagnostic interview. Results: GPS predicted drinking frequency (b = 0.109; 95% CI = 0.051, 0.167), intoxication frequency (b = 0.111; 95% CI = 0.054, 0.168), and AD symptoms (b = 0.123; 95% CI = 0.064, 0.182). Relationship moderated the association between GPS and drinking frequency (b = -0.105; 95% CI = -0.211, -0.001), intoxication frequency (b = -0.118; 95% CI = -0.220, -0.015), and AD symptoms (b = -0.119; 95% CI = -0.229, -0.010). The interaction for drinking frequency was not significant after correcting for covariates. There was a 3-way interaction between sex, relationship status, and GPS for intoxication frequency (b = 0.223; 95% CI = 0.014, 0.432), with the two-way interaction of relationship status and PRS on intoxication frequency being significant only in men. Conclusions and Relevance: Being in a relationship reduced the association between genetic predisposition and high risk drinking. Part of the protective effect of committed partnerships on alcohol misuse observed in epidemiological research may be in limiting genetic liability. However, this protective effect was largely limited to males, mapping onto earlier findings suggesting that males benefit more from romantic partnerships.