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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 The Associations Between Polygenic Risk, Sensation Seeking, Social Support, and Alcohol Use in Adulthood(Amer Psychological Assoc, 2021) Su, Jinni; Kuo, Sally I-Chun; Aliev, Fazil; Chan, Grace; Edenberg, Howard J.; Kamarajan, Chella; McCutcheon, Vivia V.Genetic predispositions play an important role in alcohol use. Understanding the psychosocial mechanisms through which genetic risk unfolds to influence alcohol use outcomes is critical for identifying modifiable targets and developing prevention and intervention efforts. In this study, we examined the role of sensation seeking and social support from family and friends in linking genetic risk to alcohol use. We also examined the role of social support in moderating the associations between genetic risk and sensation seeking and alcohol use. Data were drawn from a sample of 2,836 European American adults from the Collaborative Study on the Genetics of Alcoholism (46% male, mean age = 35.65, standard deviation [SD] = 10.78). Results from path analysis indicated that genome-wide polygenic scores for alcohol consumption (alc-GPS) were associated with higher sensation seeking, which in turn was associated with higher levels of alcohol use. alc-GPS was also associated with higher alcohol use indirectly via lower levels of family support. In addition, high friend support attenuated the association between alc-GPS and sensation seeking and alcohol use. The pattern of associations was similar for males and females, with some differences in the associations between social support and alcohol use observed across age. Our findings highlight the important role of intermediate phenotypes and gene-environment interplay in the pathways of risk from genetic predispositions to complex alcohol use outcomes.Öğe A Brief Critique of the TATES Procedure(Springer, 2018) Aliev, Fazil; Salvatore, Jessica E.; Agrawal, Arpana; Almasy, Laura; Chan, Grace; Edenberg, Howard J.; Hesselbrock, VictorThe Trait-based test that uses the Extended Simes procedure (TATES) was developed as a method for conducting multivariate GWAS for correlated phenotypes whose underlying genetic architecture is complex. In this paper, we provide a brief methodological critique of the TATES method using simulated examples and a mathematical proof. Our simulated examples using correlated phenotypes show that the Type I error rate is higher than expected, and that more TATES p values fall outside of the confidence interval relative to expectation. Thus the method may result in systematic inflation when used with correlated phenotypes. In a mathematical proof we further demonstrate that the distribution of TATES p values deviates from expectation in a manner indicative of inflation. Our findings indicate the need for caution when using TATES for multivariate GWAS of correlated phenotypes.Öğe Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial(Wiley, 2015) Albert, Dustin; Belsky, Daniel W.; Crowley, D. Max; Latendresse, Shawn J.; Aliev, Fazil; Riley, Brien; Sun, CuieEarly interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.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.Öğe Characterizations of Geometric and Discrete Pareto Distributions Based on the Conditional Distribution of kth Records(Atlantis Press, 2016) Oncel, Sevgi Yurt; Aliev, FazilThe poblem of characterizing of discrete probability distributions is an important problem. Recently many new results are obtained in characterization of distributions using kth records. Based on the distributional properties of kth weak and ordinary records some characterizations of geometric and discrete pareto distributions are given.Öğe DEPRESSION PROBLEMS AMONG TURKISH TWINS(Elsevier Science Bv, 2019) Aliev, Fazil; Oncel, Sevgi Yurt[No abstract available]Öğe 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.Öğe Exploring how Family and Neighborhood Stressors Influence Genetic Risk for Adolescent Conduct Problems and Alcohol Use(Springer/Plenum Publishers, 2020) Bares, Cristina B.; Chartier, Karen G.; Karriker-Jaffe, Katherine J.; Aliev, Fazil; Mustanski, Brian; Dick, DaniellePrevious research suggests that genetic risk factors may predispose to conduct problems and alcohol use in adolescence. Whether genetic risk factors interact with social contexts has not been well characterized among African American adolescents. Data came from a subsample of the Genes, Environment, and Neighborhood Initiative study comprising 501 African American adolescents, including 151 lifetime drinkers (56% female, mean age = 16.3, SD = 1.4). Genetic risk was assessed with polygenic risk scores for alcohol dependence. Analyses explored interactions between genetic risk and self-reported alcohol use, conduct problems, life stressors, and other covariates. The effects of two gene-environment interactions (G x E) were tested in the sample of alcohol exposed adolescents; one on conduct problems and the other on alcohol use. There were significant associations between polygenic risk for alcohol dependence and conduct problems. A significant G x E interaction showed the impact of genetic risk on conduct problems was stronger under conditions of high exposure to family and neighborhood stressors. Among this sample of African American adolescents, genetic risk for alcohol dependence was not directly associated with alcohol use but was related to more conduct problems. Further, the effect of genetic risk interacted with stressors from the family and neighborhood, so that the effect of genetic risk on conduct problems was stronger for individuals who reported greater stressors.Öğe Exploring the relationship between polygenic risk for cannabis use, peer cannabis use and the longitudinal course of cannabis involvement(Wiley, 2019) Johnson, Emma C.; Tillman, Rebecca; Aliev, Fazil; Meyers, Jacquelyn L.; Salvatore, Jessica E.; Anokhin, Andrey P.; Dick, Danielle M.Background and aims Few studies have explored how polygenic propensity to cannabis use unfolds across development, and no studies have yet examined this question in the context of environmental contributions such as peer cannabis use. Outlining the factors that contribute to progression from cannabis initiation to problem use over time may ultimately provide insights into mechanisms for targeted interventions. We sought to examine the relationships between polygenic liability for cannabis use, cannabis use trajectories from ages 12-30 years and perceived peer cannabis use at ages 12-17 years. Design Mixed-effect logistic and linear regressions were used to examine associations between polygenic risk scores, cannabis use trajectory membership and perceived peer cannabis use. Setting United States. Participants From the Collaborative Study on the Genetics of Alcoholism (COGA) study, a cohort of 1167 individuals aged 12-26 years at their baseline (i.e. first) interview. Measurements Key measurements included life-time cannabis use (yes/no), frequency of past 12-month cannabis use, maximum life-time frequency of cannabis use, cannabis use disorder (using DSM-5 criteria) and perceived peer cannabis use. Polygenic risk scores (PRS) were created using summary statistics from a large (n = 162 082) genome-wide association study (GWAS) of cannabis use. Findings Three trajectories reflecting no/low (n = 844), moderate (n = 137) and high (n = 186) use were identified. PRS were significantly associated with trajectory membership [P = 0.002-0.006, maximum conditional R-2 = 1.4%, odds ratios (ORs) = 1.40-1.49]. Individuals who reported that most/all of their best friends used cannabis had significantly higher PRS than those who reported that none of their friends were users [OR = 1.35, 95% confidence interval (CI) = 1.04, 1.75, P = 0.023]. Perceived peer use itself explained up to 11.3% of the variance in trajectory class membership (OR = 1.50-4.65). When peer cannabis use and the cannabis use PRS were entered into the model simultaneously, both the PRS and peer use continued to be significantly associated with class membership (P < 0.01). Conclusions Genetic propensity to cannabis use derived from heterogeneous samples appears to correlate with longitudinal increases in cannabis use frequency in young adults.Öğe The Family Check-up Intervention Moderates Polygenic Influences on Long-Term Alcohol Outcomes: Results from a Randomized Intervention Trial(Springer/Plenum Publishers, 2019) Kuo, Sally I-Chun; Salvatore, Jessica E.; Aliev, Fazil; Ha, Thao; Dishion, Thomas J.; Dick, Danielle M.Alcohol problems are influenced by both genetic and environmental factors. Evidence from twin models and measured gene-environment interaction studies has demonstrated that the importance of genetic influences changes as a function of the environment. Research has also shown that family-centered interventions may protect genetically susceptible youth from developing substance use problems. In this study, we brought large-scale gene identification findings into an intervention study to examine gene-by-intervention effects. Using genome-wide polygenic scores derived from an independent genome-wide association study of adult alcohol dependence, we examined whether an adolescent family-centered intervention would moderate the effect of genetic risk for alcohol dependence on lifetime alcohol dependence in young adulthood, approximately 15 years after the start of intervention, among European American (N = 271; 48.3% in the intervention condition) and African American individuals (N = 192; 51.6% in the intervention condition). We found that among European American individuals, the intervention moderated the association between alcohol dependence polygenic scores and lifetime alcohol dependence diagnosis in young adulthood. Among participants in the control condition, higher alcohol dependence polygenic scores were associated with a greater likelihood of receiving an alcohol dependence diagnosis; in contrast, among participants in the intervention condition, there was no association between alcohol dependence polygenic scores and alcohol dependence diagnosis. No moderation effect was found among African Americans. These results demonstrate that modifying environments of genetically vulnerable youth could reduce the likelihood of developing alcohol dependence and underscore the significance of environmentally focused prevention and intervention efforts.Öğe Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence Symptoms Among Young Adults(Alcohol Res Documentation Inc Cent Alcohol Stud Rutgers Univ, 2015) Long, Elizabeth C.; Aliev, Fazil; Wang, Jen-Chyong; Edenberg, Howard J.; Nurnberger, John, Jr.; Hesselbrock, Victor; Porjesz, BerniceObjective: The gene GRM8, a metabotropic glutamate receptor, has emerged as a gene of interest for its possible role in the development of alcohol dependence, with evidence of association with an electrophysiological endophenotype and level of response to alcohol as well as suggestive evidence of association with alcohol dependence. Method: The present study further investigated the association between GRM8 and alcohol dependence symptom counts among young adults using a new sample of individuals collected as part of the prospective sample (ages 18-26 years; N = 842) from the Collaborative Study on the Genetics of Alcoholism (COGA). Results: Two single-nucleotide polymorphisms were significantly associated with alcohol dependence in European Americans using the Nyholt corrected p value of .007: rs886003 (beta = -.212, p =.0002) and rs17862325 (beta = -.234, p < .0001), but not in African Americans, likely because of the lower power to detect association in this group. Conclusions: These results further implicate the role of glutamate receptor genes such as GRM8 in the development of alcohol dependence.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 Associated With Alcohol Outcomes Show Enrichment of Effects With Broad Externalizing and Impulsivity Phenotypes in an Independent Sample(Alcohol Res Documentation Inc Cent Alcohol Stud Rutgers Univ, 2015) Aliev, Fazil; Wetherill, Leah; Bierut, Laura; Bucholz, Kathleen K.; Edenberg, Howard; Foroud, Tatiana; Dick, Danielle M.Objective: The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult individuals (N=2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman's Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability. Method: We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes. Results: For all phenotypes, there was significant enrichment of association results (p<.05) compared with chance expectations. The greatest number of significant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p<.05 with Sensation Seeking was significantly greater than that observed for each of the other phenotypes. Conclusions: We find evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we fmd significant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems.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 Genetic and environmental etiology of drinking motives in college students(Wiley, 2022) Savage, Jeanne E.; Peterson, Roseann E.; Aliev, Fazil; Dick, Danielle M.Background Drinking motives are robust proximal predictors of alcohol use behaviors and may mediate distinct etiological pathways in the development of alcohol misuse. However, little is known about the genetic and environmental etiology of drinking motives themselves and their potential utility as endophenotypes. Methods Here, we leverage a longitudinal study of college students from diverse racial/ethnic backgrounds (phenotypic N = 9889, genotypic N = 4855) to investigate the temporal stability and demographic and environmental predictors of four types of drinking motives (enhancement, social, coping, and conformity). Using genome-wide association study (GWAS) and in silico tools, we characterize their associated genes and genetic variants (single nucleotide polymorphisms or SNPs). Results Drinking motives were stable across four years of college (ICC >0.74). Some robust environmental predictors of alcohol misuse (parental autonomy granting and peer deviance) were broadly associated with multiple types of drinking motives, while others (e.g., trauma exposure) were type specific. Genome-wide analyses indicated modest SNP-based heritability (14-22%, n.s.) and several suggestive genomic loci that corroborate findings from previous molecular genetic studies (e.g., PECR and SIRT4 genes), indicating possible differences in the genetic etiology of positive versus negative reinforcement drinking motives that align with an internalizing/externalizing typology of alcohol misuse. Coping motives were significantly genetically correlated with alcohol use disorder diagnoses (r(g) = 0.71, p = 0.001). However, results from the genetic analyses were largely underpowered to detect significant associations. Conclusions Drinking motives show promise as endophenotypes but require further investigation in larger samples to further our understanding of the etiology of alcohol misuse.Öğe The Genetic Relationship Between Alcohol Consumption and Aspects of Problem Drinking in an Ascertained Sample(Wiley, 2019) Johnson, Emma C.; St Pierre, Celine L.; Meyers, Jacquelyn L.; Aliev, Fazil; McCutcheon, Vivia V.; Lai, Dongbing; Dick, Danielle M.Background Genomewide association studies (GWAS) have begun to identify loci related to alcohol consumption, but little is known about whether this genetic propensity overlaps with specific indices of problem drinking in ascertained samples. Methods In 6,731 European Americans who had been exposed to alcohol, we examined whether polygenic risk scores (PRS) from a GWAS of weekly alcohol consumption in the UK Biobank predicted variance in 6 alcohol-related phenotypes: alcohol use, maximum drinks within 24 hours (MAXD), total score on the Self-Rating of the Effects of Ethanol Questionnaire (SRE-T), DSM-IV alcohol dependence (DSM4AD), DSM-5 alcohol use disorder symptom counts (DSM5AUDSX), and reduction/cessation of problematic drinking. We also examined the extent to which an single nucleotide polymorphism (rs1229984) in ADH1B, which is strongly associated with both alcohol consumption and dependence, contributed to the polygenic association with these phenotypes and whether PRS interacted with sex, age, or family history of alcoholism to predict alcohol-related outcomes. We performed mixed-effect regression analyses, with family membership and recruitment site included as random effects, as well as survival modeling of age of onset of DSM4AD. Results PRS for alcohol consumption significantly predicted variance in 5 of the 6 outcomes: alcohol use (Delta marginal R-2 = 1.39%, Delta area under the curve [AUC] = 0.011), DSM4AD (Delta marginal R-2 = 0.56%; Delta AUC = 0.003), DSM5AUDSX (Delta marginal R-2 = 0.49%), MAXD (Delta marginal R-2 = 0.31%), and SRE-T (Delta marginal R-2 = 0.22%). PRS were also associated with onset of DSM4AD (hazard ratio = 1.11, p = 2.08e-5). The inclusion of rs1229984 attenuated the effects of the alcohol consumption PRS, particularly for DSM4AD and DSM5AUDSX, but the PRS continued to exert an independent effect for all 5 alcohol measures (Delta marginal R-2 after controlling for ADH1B = 0.14 to 1.22%). Interactions between PRS and sex, age, or family history were nonsignificant. Conclusions Genetic propensity for typical alcohol consumption was associated with alcohol use and was also associated with 4 of the additional 5 outcomes, though the variance explained in this sample was modest. Future GWAS that focus on the multifaceted nature of AUD, which goes beyond consumption, might reveal additional information regarding the polygenic underpinnings of problem drinking.Öğe Genome-Wide Association of Heroin Dependence in Han Chinese(Public Library Science, 2016) Kalsi, Gursharan; Euesden, Jack; Coleman, Jonathan R. I.; Ducci, Francesca; Aliev, Fazil; Newhouse, Stephen J.; Liu, XieheDrug addiction is a costly and recurring healthcare problem, necessitating a need to understand risk factors and mechanisms of addiction, and to identify new biomarkers. To date, genome-wide association studies (GWAS) for heroin addiction have been limited; moreover they have been restricted to examining samples of European and African-American origin due to difficulty of recruiting samples from other populations. This is the first study to test a Han Chinese population; we performed a GWAS on a homogeneous sample of 370 Han Chinese subjects diagnosed with heroin dependence using the DSM-IV criteria and 134 ethnically matched controls. Analysis using the diagnostic criteria of heroin dependence yielded suggestive evidence for association between variants in the genes CCDC42 (coiled coil domain 42; p = 2.8x10(-7)) and BRSK2 (BR serine/threonine 2; p = 4.110(-6)). In addition, we found evidence for risk variants within the ARHGEF10 (Rho guanine nucleotide exchange factor 10) gene on chromosome 8 and variants in a region on chromosome 20q13, which is gene-poor but has a concentration of mRNAs and predicted miRNAs. Gene-based association analysis identified genome-wide significant association between variants in CCDC42 and heroin addiction. Additionally, when we investigated shared risk variants between heroin addiction and risk of other addiction-related and psychiatric phenotypes using polygenic risk scores, we found a suggestive relationship with variants predicting tobacco addiction, and a significant relationship with variants predicting schizophrenia. Our genome wide association study of heroin dependence provides data in a novel sample, with functionally plausible results and evidence of genetic data of value to the field.Öğe Genome-wide association study identifies 48 common genetic variants associated with handedness(Nature Portfolio, 2021) Cuellar-Partida, Gabriel; Tung, Joyce Y.; Eriksson, Nicholas; Albrecht, Eva; Aliev, Fazil; Andreassen, Ole A.; Barroso, InesHandedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 x 10(-8)) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r(G) = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders. A genome-wide association study of 1.7 million individuals identified 41 genetic variants associated with left-handedness and 7 associated with ambidexterity. The genetic correlation between the traits was low, thereby implying different aetiologies.
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