Polygenic risk for alcohol misuse is moderated by romantic partnerships

Abstract

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.

Predicting alcohol use from genome-wide polygenic scores, environmental factors, and their interactions in young adulthood

“…Alcohol Use Disorder Identification Test (AUDIT) scores (Kranzler et al, 2019; Sanchez-Roige et al, 2019)). GPS based on these GWA studies predict alcohol use, with the variance accounted for ranging from 0.1% to 2.5% (Barr, Kuo et al 2019; Liu, Jiang et al 2019; Mies, Verweij et al 2018; Schumann, Liu et al 2016). In general, the predictive power of a GPS depends on the GWA sample size, SNP heritability of the trait, selection thresholds for selecting markers for creating the score, etc., among many other factors (Dudbridge, 2013).…”

Multivariable G-E interplay in the prediction of educational achievement

“…A GPS derived from a genome-wide association study of educational attainment (years of schooling) (16) predicts up to 15% of the variance of EA (17). As more powerful GPS become available, they have begun to be used widely in research on GxE (18)(19)(20)(21)(22)(23) and rGE (7,(24)(25)(26)(27).…”

Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples

“…Finally, these analyses examined the marginal influence of PRS, independent of environment. Processes of gene-environment interaction (GxE) are well documented in alcohol misuse [44][45][46][47] . Incorporating environmental information along with PRS in a methodologically rigorous manner will be an important next step in developing clinically predictive algorithms.…”