Finding genes involved in complex behavioral outcomes, and understanding the pathways by which they confer risk, is a challenging task, necessitating large samples that are phenotypically well characterized across time. We describe an effort to create a university-wide research project aimed at understanding how genes and environments impact alcohol use and related substance use and mental health outcomes across time in college students. Nearly 70% of the incoming freshman class (N = 2715) completed on-line surveys, with 80% of the students from the fall completing spring follow-ups. 98% of eligible participants also gave DNA. The participants closely approximated the university population in terms of gender and racial/ethnic composition. Here we provide initial results on alcohol use outcomes from the first wave of the sample, as well as associated predictor variables. We discuss the potential for this kind of research to advance our understanding of genetic and environment influences on substance use and mental health outcomes.
As psychiatric genetics enters an era where gene identification is finally yielding robust, replicable genetic associations and polygenic risk scores, it is important to consider next steps and delineate how that knowledge will be applied to ultimately ameliorate suffering associated with substance use and psychiatric disorders. Much of the post-genome-wide association study discussion has focused on the potential of genetic information to elucidate the underlying biology and use this information for the development of more effective pharmaceutical treatments. In this review we focus on additional areas of research that should follow gene identification. By taking genetic findings into longitudinal, developmental studies, we can map the pathways by which genetic risk manifests across development, elucidating the early behavioral manifestations of risk, and studying how various environments and interventions moderate that risk across developmental stages. The delineation of risk across development will advance our understanding of mechanism, sex differences and risk and resilience processes in different racial/ethnic groups. Here, we review how the extant twin study literature can be used to guide these efforts. Together, these new lines of research will enable us to develop more informed, tailored prevention and intervention efforts.
Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk.Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults.Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample.Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1 impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification.
Background: Peer drinking is one of the most robust predictors of college students' alcohol use and can moderate students' genetic risk for alcohol use. Peer effect research generally suffers from 2 problems: selection into peer groups and relying more on perceptions of peer alcohol use than peers' selfreport. The goal of the present study was to overcome those limitations by capitalizing on a genetically informed sample of randomly assigned college roommates to examine multiple dimensions of peer influence and the interplay between peer effects and genetic predisposition on alcohol use, in the form of polygenic scores.Methods: We used a subsample (n = 755) of participants from a university-wide, longitudinal study at a large, diverse, urban university. Participants reported their own alcohol use during fall and spring and their perceptions of college peers' alcohol use in spring. We matched individuals into their rooms and residence halls to create a composite score of peer-reported alcohol use for each of those levels. We examined multiple dimensions of peer influence and whether peer influence moderated genetic predisposition to predict college students' alcohol use using multilevel models to account for clustering at the room and residence hall level.Results: We found that polygenic scores (b = 0.12), perceptions of peer drinking (b = 0.37), and roommates' self-reported drinking (b = 0.10) predicted alcohol use (all ps < 0.001), while average alcohol use across residence hall did not (b = À0.01, p = 0.86). We found no evidence for interactions between peer influence and genome-wide polygenic scores for alcohol use.Conclusions: Our findings underscore the importance of genetic predisposition on individual alcohol use and support the potentially causal nature of the association between peer influence and alcohol use.
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