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Öğe Alcohol Metabolizing Polygenic Risk for Alcohol Consumption in European American College Students(Alcohol Res Documentation Inc Cent Alcohol Stud Rutgers Univ, 2018) Thomas, Nathaniel S.; Adkins, Amy; Aliev, Fazil; Edwards, Alexis C.; Webb, Bradley T.; Tiarsmith, E. Clare; Kendler, Kenneth S.Objective: Evidence suggests that the nature and magnitude of some genetic effects on alcohol use vary by age. We tested for moderation in the effect of an alcohol metabolizing polygenic score by time across the college years. Method: Participants (total n = 2,214) were drawn from three cohorts of undergraduate college students, who were assessed annually for up to 4 years starting in their freshman year. Polygenic risk scores (PRSs) were calculated from genes involved in the metabolism of alcohol, as many of these markers are among the best replicated in association studies examining alcohol use phenotypes. Linear mixed effects models were fit by maximum likelihood to test the main effects of time and the PRS on alcohol consumption, as well as moderation of the PRS effect on alcohol consumption by time. Results: In the main effects model, the fixed effects for time and the PRS were positively associated with alcohol consumption. The interaction term testing moderation of the PRS effect by time reached statistical significance and remained statistically significant after other relevant interaction effects were controlled for. The main effect of the PRS accounted for 0.2% of the variance in alcohol consumption, whereas the interaction of PRS effect and time accounted for 0.05%. Conclusions: Alcohol metabolizing genetic effects on alcohol use appear to be more influential in later years of college than in earlier years. Shifting environmental contexts, such as increased access to alcohol as individuals approach the legal age to purchase alcohol, may account for this association.Öğe Associations between the CADM2 gene, substance use, risky sexual behavior, and self-control: A phenome-wide association study(Wiley, 2021) Arends, Rachel M.; Pasman, Joelle A.; Verweij, Karin J. H.; Derks, Eske M.; Gordon, Scott D.; Hickie, Ian; Thomas, Nathaniel S.Risky behaviors, such as substance use and unprotected sex, are associated with various physical and mental health problems. Recent genome-wide association studies indicated that variation in the cell adhesion molecule 2 (CADM2) gene plays a role in risky behaviors and self-control. In this phenome-wide scan for risky behavior, it was tested if underlying common vulnerability could be (partly) explained by pleiotropic effects of this gene and how large the effects were. Single nucleotide polymorphism (SNP)-level and gene-level association tests within four samples (25 and Up, Spit for Science, Netherlands Twin Register, and UK Biobank and meta-analyses over all samples (combined sample of 362,018 participants) were conducted to test associations between CADM2, substance- and sex-related risk behaviors, and various measures related to self-control. We found significant associations between the CADM2 gene, various risky behaviors, and different measures of self-control. The largest effect sizes were found for cannabis use, sensation seeking, and disinhibition. Effect sizes ranged from 0.01% to 0.26% for single top SNPs and from 0.07% to 3.02% for independent top SNPs together, with sufficient power observed only in the larger samples and meta-analyses. In the largest cohort, we found indications that risk-taking proneness mediated the association between CADM2 and latent factors for lifetime smoking and regular alcohol use. This study extends earlier findings that CADM2 plays a role in risky behaviors and self-control. It also provides insight into gene-level effect sizes and demonstrates the feasibility of testing mediation. These findings present a good starting point for investigating biological etiological pathways underlying risky behaviors.Öğe Cannabis use in college: genetic predispositions, peers, and activity participation(Springer, 2020) Thomas, Nathaniel S.; Salvatore, Jessica E.; Gillespie, Nathan A.; Aliev, Fazil; Ksinan, Albert J.; Dick, Danielle M.[No abstract available]Öğe Cannabis use in college: Genetic predispositions, peers, and activity participation(Elsevier Ireland Ltd, 2021) Thomas, Nathaniel S.; Salvatore, Jessica E.; Gillespie, Nathan A.; Aliev, Fazil; Ksinan, Albert J.; Dick, Danielle M.Background: Among adult college students in the US, cannabis use is common and associated with considerable negative consequences to health, cognition, and academic functioning, underscoring the importance of identifying risk and protective factors. Cannabis use is influenced by genetic factors, but genetic risk is not determinative. Accordingly, it is critical to identify environments that reduce risk among those who are at elevated genetic risk. This study examined the impact of polygenic scores for cannabis initiation, various forms of social activity participation, and peer deviance on recent cannabis use. Our aim was to test whether these environments moderate genetic risk for cannabis use. Methods: Data came from a longitudinal sample of undergraduate college students of European American (EA; N-EA = 750) and African American (AA; N-AA = 405) ancestry. Generalized estimating equations with a logit link function were used to examine main effects and two-way interactions. Results: Engagement with church activities was associated with lower probability of cannabis use. Peer deviance was associated with higher probability of cannabis use. Engagement with community activities moderated the influence of the polygenic risk score in the EA sample, such that PRS was associated with recent cannabis use among those who never engaged in community activities. This effect did not replicate in AAs, which may have been due to the portability of PRS based on EA discovery samples. Conclusions: Results suggest that community activities may limit the influence of genetic risk, as associations between PRS and cannabis use were only observed among individuals who never engaged in community activities.
