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    Education and alcohol use: A study of gene-environment interaction in young adulthood
    (Pergamon-Elsevier Science Ltd, 2016) Barr, Peter B.; Salvatore, Jessica E.; Maes, Hermine; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J.
    The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one's position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
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    Polygenic risk for alcohol misuse is moderated by romantic partnerships
    (Wiley, 2019) Barr, Peter B.; Kuo, Sally I-Chun; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard J.; Kaprio, Jaakko
    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 x E) and (3) whether G x 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.
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    Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis
    (Wiley, 2020) Salvatore, Jessica E.; Barr, Peter B.; Stephenson, Mallory; Aliev, Fazil; Kuo, Sally I-Chun; Su, Jinni; Agrawal, Arpana
    Background and Aims The associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis). Design Polygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families. Setting Six sites in the United States. Participants European ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample. Measurements Outcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerstrom nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment. Findings In polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R-2) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R-2 0.13-0.20%). Conclusions Individuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education).
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    Social Relationships Moderate Genetic Influences on Heavy Drinking in Young Adulthood
    (Alcohol Res Documentation Inc Cent Alcohol Stud Rutgers Univ, 2017) Barr, Peter B.; Salvatore, Jessica E.; Maes, Hermine H.; Korhonen, Tellervo; Latvala, Antti; Aliev, Fazil; Viken, Richard
    Objective: Social relationships, such as committed partnerships, limit risky behaviors like heavy drinking, in part, because of increased social control. The current analyses examine whether involvement in committed relationships or social support extend beyond a main effect to limit genetic liability in heavy drinking (gene-environment interaction) during young adulthood. Method: Using data from the young adult wave of the Finnish Twin Study, FinnTwin 12 (n = 3,269), we tested whether involvement in romantic partnerships or social support moderated genetic influences on heavy drinking using biometric twin modeling for gene-environment interaction. Results: Involvement in a romantic partnership was associated with a decline in genetic variance in both males and females, although the overall magnitude of genetic influence was greater in males. Sex differences emerged for social support: increased social support was associated with increased genetic influence for females and reduced genetic influence for males. Conclusions: These findings demonstrate that social relationships are important moderators of genetic influences on young adult alcohol use. Mechanisms of social control that are important in limiting genetic liability during adolescence extend into young adulthood. In addition, although some relationships limit genetic liability equally, others, such as extensive social networks, may operate differently across sex.
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    Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples
    (Nature Publishing Group, 2020) Barr, Peter B.; Ksinan, Albert; Su, Jinni; Johnson, Emma C.; Meyers, Jacquelyn L.; Wetherill, Leah; Latvala, Antti
    Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain similar to 2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.