This COMRAD application continues a multisite collaboration, initiated under DA 012845, to conduct a prospective study to address critical issues in the genetic epidemiology of adolescent onset antisocial drug dependence. Addressing these issues requires sample sizes greater than a single site can reasonably attain, as well as the multidisciplinary expertise, of psychiatrists, psychologists, and behavioral and molecular geneticists, that is difficult to provide at a single site. Our rationale for focusing on persistent antisocial substance dependence that has its onset in adolescence is the guiding hypothesis that early onset, persistent, and pervasive behavior will reflect a biological vulnerability of the individual. We propose to conduct genetic and clinical descriptive studies of adolescent-onset antisocial drug dependence in the largest samples ever studied prospectively for this condition. With our Center sample (Center on Antisocial Drug Dependence, DA011015), this multisite collaboration will yield a total of approximately 800 probands with adolescent-onset substance and conduct problems, together with their siblings, re-assessed at five-year follow-up. We anticipate a final sample of ~600 persistent cases and ~200 non-persistent former cases, together with their siblings, and a sample of 600 community control subjects and their siblings (drawn from our existing community samples). To achieve this, we will complete the five-year follow-up of 1186 clinical probands and their siblings on whom we have Wave 1 assessments (Aim 1). We expect a 70 percent follow-up rate, which will yield a sample of 830 clinical probands aged 19 though 23 years at follow-up, and their siblings. Of these probands, 251 will be completed, at no cost to this application, as part of DA011015. The COMRAD will be funded to complete phenotypic assessements of the remaining 579 probands and their siblings and to carry out the following analyses of the entire sample.
Aim 2 : 1) Key predictors which were assessed during the adolescent assessment will be examined to determine whether they discriminate between proband cases that persist in their antisocial and substance use behaviors versus those cases that desist. 2) We will examine trajectories of adolescent substance use and antisocial behaviors and examine the role of contextual factors such as critical life transitions on the development of these behaviors. 3) We will explore possible new phenotypes by testing them for maximal heritability in the community samples and examining the patterns of familial transmission in the clinical samples.
Aim 3 : We will conduct genome wide, family-based, association analyses of persistent adolescent-onset antisocial drug dependence, using the ~600 persistent cases and their siblings, and ~600 controls and their siblings, and parental DNA when available.

Public Health Relevance

Substance abuse/use disorder is a significant social and health problem. This multisite collaborative study of persistent adolescent-onset antisocial drug dependence provides a unique opportunity to assess differing developmental trajectories and clinical courses, the role of comorbidity, early onset, familial loading, and genetic influences on these behaviors.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Rutter, Joni
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado at Boulder
Other Domestic Higher Education
United States
Zip Code
Border, Richard; Corley, Robin P; Brown, Sandra A et al. (2018) Independent predictors of mortality in adolescents ascertained for conduct disorder and substance use problems, their siblings and community controls. Addiction 113:2107-2115
Curry, Inga; Trim, Ryan S; Brown, Sandra A et al. (2018) Positive expectancies mediate the association between sensation seeking and marijuana outcomes in at-risk young adults: A test of the acquired preparedness model. Am J Addict :
Curry, Inga; Luk, Jeremy W; Trim, Ryan S et al. (2018) Impulsivity Dimensions and Risky Sex Behaviors in an At-Risk Young Adult Sample. Arch Sex Behav 47:529-536
Melroy-Greif, Whitney E; Simonson, Matthew A; Corley, Robin P et al. (2017) Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans. Nicotine Tob Res 19:417-425
Luk, Jeremy W; Trim, Ryan S; Karyadi, Kenny A et al. (2017) Unique and interactive effects of impulsivity facets on reckless driving and driving under the influence in a high-risk young adult sample. Pers Individ Dif 114:42-47
Luk, Jeremy W; Worley, Matthew J; Winiger, Evan et al. (2016) Risky driving and sexual behaviors as developmental outcomes of co-occurring substance use and antisocial behavior. Drug Alcohol Depend 169:19-25
Coors, Marilyn E; Raymond, Kristen M; Hopfer, Christian J et al. (2016) Adolescents with substance use disorder and assent/consent: Empirical data on understanding biobank risks in genomic research. Drug Alcohol Depend 159:267-71
Kamens, Helen M; Corley, Robin P; Richmond, Phillip A et al. (2016) Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence. Behav Genet 46:693-704
Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun et al. (2016) Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet 46:151-69
Choi, Tai Kiu; Worley, Matthew J; Trim, Ryan S et al. (2016) Effect of adolescent substance use and antisocial behavior on the development of early adulthood depression. Psychiatry Res 238:143-149

Showing the most recent 10 out of 73 publications