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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA012845-09
Application #
8017431
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Wideroff, Louise
Project Start
2000-09-15
Project End
2012-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
9
Fiscal Year
2011
Total Cost
$668,942
Indirect Cost
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
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 238:143-9
Melroy-Greif, Whitney E; Simonson, Matthew A; Corley, Robin P et al. (2016) Examination of the Involvement of Cholinergic-Associated Genes in Nicotine Behaviors in European and African Americans. Nicotine Tob Res :
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
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
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
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
Melroy-Greif, Whitney E; Vadasz, Csaba; Kamens, Helen M et al. (2016) Test for association of common variants in GRM7 with alcohol consumption. Alcohol 55:43-50
Derringer, Jaime; Corley, Robin P; Haberstick, Brett C et al. (2015) Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample. Behav Genet 45:375-81
Coors, Marilyn E; Raymond, Kristen M; McWilliams, Shannon K et al. (2015) What adolescents enrolled in genomic addiction research want to know about conflicts of interest. Drug Alcohol Depend 147:272-5
Trim, Ryan S; Worley, Matthew J; Wall, Tamara L et al. (2015) Bivariate Trajectories of Substance Use and Antisocial Behavior: Associations with Emerging Adult Outcomes in a High-Risk Sample. Emerg Adulthood 3:265-276

Showing the most recent 10 out of 69 publications