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    Predicting Alcohol Dependence Symptoms by Young Adulthood: A Co-Twin Comparisons Study
    (Cambridge Univ Press, 2021) Stephenson, Mallory; Barr, Peter; Aliev, Fazil; Ksinan, Albert; Latvala, Antti; Vuoksimaa, Eero; Viken, Richard
    Co-twin comparisons address familial confounding by controlling for genetic and environmental influences that twin siblings share. We applied the co-twin comparison design to investigate associations of adolescent factors with alcohol dependence (AD) symptoms. Participants were 1286 individuals (581 complete twin pairs; 42% monozygotic; and 54% female) from the FinnTwin12 study. Predictors included adolescent academic achievement, substance use, externalizing problems, internalizing problems, executive functioning, peer environment, physical health, relationship with parents, alcohol expectancies, life events, and pubertal development. The outcome was lifetime AD clinical criterion count, as measured in young adulthood. We examined associations of each adolescent domain with AD symptoms in individual-level and co-twin comparison analyses. In individual-level analyses, adolescents with higher levels of substance use, teacher-reported externalizing problems at age 12, externalizing problems at age 14, self- and co-twin-reported internalizing problems, peer deviance, and perceived difficulty of life events reported more symptoms of AD in young adulthood (ps < .044). Conversely, individuals with higher academic achievement, social adjustment, self-rated health, and parent-child relationship quality met fewer AD clinical criteria (ps < .024). Associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, self-rated health, and AD symptoms were of a similar magnitude in co-twin comparisons. We replicated many well-known adolescent correlates of later alcohol problems, including academic achievement, substance use, externalizing and internalizing problems, self-rated health, and features of the peer environment and parent-child relationship. Furthermore, we demonstrate the utility of co-twin comparisons for understanding pathways to AD. Effect sizes corresponding to the associations between adolescent substance use, teacher-reported externalizing problems, co-twin-reported internalizing problems, peer deviance, and self-rated health were not significantly attenuated (p value threshold = .05) after controlling for genetic and environmental influences that twin siblings share, highlighting these factors as candidates for further research.
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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.
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    Which adolescent factors predict alcohol misuse in young adulthood? A co-twin comparisons study
    (Wiley, 2020) Stephenson, Mallory; Barr, Peter; Ksinan, Albert; Aliev, Fazil; Latvala, Antti; Viken, Richard; Rose, Richard
    Background and aims Research on adolescent predictors of later alcohol misuse is typically conducted on samples of singletons, and associations may be confounded by between-family differences. To address potential confounding, we applied a co-twin comparison design to evaluate whether differences between co-twins in a wide array of adolescent risk factors predicted differences in young adult alcohol misuse. Design Longitudinal study in which associations between characteristics of the sample as adolescents were used to predict young adult alcohol misuse in individual-level analyses and co-twin comparisons. Setting Finland. Participants A total of 3402 individuals (1435 complete twin pairs; 36% monozygotic; 57% female) from the FinnTwin12 study. Measurements The young adult alcohol misuse outcome was a composite score of alcohol use and intoxication frequency. Adolescent predictors included factor scores representing academic performance, substance use, externalizing problems, internalizing problems, peer environment, physical health and relationship with parents; and single measures tapping alcohol expectancies, life events and pubertal development. Findings In individual-level analyses, individuals with higher adolescent substance use, externalizing problems, time with friends, peer deviance, sports involvement, sleeping difficulties, parental discipline, positive alcohol expectancies and difficulty of life events reported higher alcohol misuse in young adulthood (Ps < 0.019, R-2 = 0.0003-0.0310%). Conversely, those with higher adolescent internalizing problems, parent-child relationship quality and time with parents reported lower alcohol misuse (Ps < 0021, R-2 = 0.0018-0.0093%). The associations with adolescent substance use and alcohol expectancies remained significant in co-twin comparisons (Ps < 0.049, R-2 = 0.0019-0.0314%). Further, academic performance emerged as a significant predictor, such that individuals with higher grades compared with their co-twin reported higher young adult alcohol misuse (Ps < 0.029, R-2 = 0.0449-0.0533%). Conclusions Adolescent substance use, positive alcohol expectancies and higher academic performance appear to be robust predictors of later alcohol misuse.