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Öğe GENE-BY-INTERVENTION EFFECTS ON ALCOHOL DEPENDENCE SYMPTOMS IN EMERGING ADULTHOOD(Elsevier, 2019) Neale, Zoe; Kuo, Sally I-Chun; Aliev, Fazil; Barr, Peter; Su, Jinni; Elam, Kit; Ha, Thao[No abstract available]Öğe Genes, Roommates, and Residence Halls: A Multidimensional Study of the Role of Peer Drinking on College Students' Alcohol Use(Wiley, 2019) Smith, Rebecca L.; Salvatore, Jessica E.; Aliev, Fazil; Neale, Zoe; Barr, Peter; Dick, Danielle M.; Pedersen, KimberlyBackground 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' self-report. 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 (beta = 0.12), perceptions of peer drinking (beta = 0.37), and roommates' self-reported drinking (beta = 0.10) predicted alcohol use (all ps < 0.001), while average alcohol use across residence hall did not (beta = -0.01, 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.Öğe Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems(Wiley, 2018) Salvatore, Jessica E.; Savage, Jeanne E.; Barr, Peter; Wolen, Aaron R.; Aliev, Fazil; Vuoksimaa, Eero; Latvala, AnttiBackgroundCharacterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (GxE) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit GxE effects. MethodsWe examined these questions in the young adult FinnTwin12 sample (n=1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the GxE analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant GxE effects in an interaction between romantic relationship status and intoxication frequency. ResultsContrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In GxE models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. ConclusionsThese findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.Öğe 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, RichardCo-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.Öğe RISK PREDICTION WITH POLYGENIC RISK SCORES IN MULTI-ETHNIC SAMPLES(Elsevier, 2019) Aliev, Fazil; Salvatore, Jessica; Su, Jinni; Kuo, Sally I-Chun; Barr, Peter; Agrawal, Arpana; Cho, Seung Bin[No abstract available]Öğe 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, RichardBackground 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.
