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. Key Points Question Do romantic relationships moderate polygenic risk on alcohol misuse in young adulthood? Findings Involvement in romantic relationships moderated the polygenic risk on frequency of intoxication and DSM-IV alcohol dependence symptoms, such that polygenic associations with alcohol misuse were stronger among those not in a romantic relationship. Males experienced a stronger protective effect of romantic relationship in limiting the manifestation of genetic predispositions toward intoxication frequency. Meaning The interplay between genes and environment is important in understanding etiology of problematic alcohol use, and romantic relationships appear to buffer genetic risk for alcohol misuse in young adulthood. Findings underscore how social relationships may alter the risk posed by genetic predispositions.