Polygenic Risk for Alcohol Misuse is Moderated by Romantic Partnerships: Relationships Moderate Polygenic Risk Scores

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.