Polygenic risk for alcohol misuse is moderated by romantic partnerships

Background and Aims: Previous twin research suggests relationship status can moderate underlying genetic liability towards alcohol misuse. This paper examined: (1) whether genome-wide polygenic scores (GPS) for alcohol consumption are associated with alcohol misuse; (2) whether these GPS are moderated by romantic relationships (gene–environment interaction; G × E) and (3) whether G × E results are consistent across sex. Design: Linear mixed-effects models were used to test associations between genome-wide polygenic scores, relationship status and alcohol use/misuse. Setting: Finnish twins born between 1983 and 1987 identified through Finland's central population registry. Participants: An intensively studied subset of Finnish Twin Study (FinnTwin12) during the young adult phase (aged 20–26 years). The analytical sample includes those with complete interview and genetic data (n = 1201). Measurements: Key measurements included involvement in a romantic partnership, drinking frequency, intoxication frequency and DSM-IV alcohol dependence (AD) symptoms. Genome-wide polygenic scores (GPS) were created from available summary statistics from a large genome-wide association study (GWAS) of drinks per week. Results: GPS predicted drinking frequency [b = 0.109; 95% confidence interval (CI) = 0.050, 0.168], intoxication frequency (b = 0.111; 95% CI = 0.054, 0.168) and AD symptoms (b = 0.123; 95% CI = 0.064, 0.182). Having a romantic relationship negatively influenced 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, −0.016) and AD symptoms (b = −0.119; 95% CI = −0.229, −0.009). There was a three-way interaction between sex, relationship status and GPS for intoxication frequency (b = 0.223; 95% CI = 0.013, 0.433), such that the reduced association between GPS and intoxication frequency for those in a relationship was only apparent in males. We found no evidence of three-way interactions for drinking frequency or AD symptoms. Conclusions: Being in a romantic relationship reduced the association between genetic predisposition and drinking, high-risk drinking and alcohol problems. However, for high-risk drinking the protective effect was limited to males, mapping onto earlier findings suggesting that males benefit more from romantic partnerships.