Substance Abuse and the Dopamine System Genes
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Substance Abuse and the Dopamine System Genes |
This is a project funded by the National Institute on Drug Abuse (grant number R01 DA011922). The study has joined the NIDA Genetics Consortium, a group originally consisting of studies funded under RFA DA-99-003, "Genetics of Drug Abuse Vulnerability" (see also information for the NIDA Genetics Workgroup). The primary goal of this research is to examine the contribution and interaction of DNA polymorphisms, personality and environmental factors in variation in the liability to substance dependence. The study is conducted under the aegis of the Center for Education and Drug Abuse Research (CEDAR), School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania.
Aims
Aim 1. Evaluate known polymorphisms at the dopamine receptor and MAOA genes, separately and as haplotypes, for their association with the liability to substance dependence (SD) in 350 families ascertained via an adolescent male with a DSM-IV diagnosis of SD, and in adult case-control male and female samples (250 SD and 250 controls from the CEDAR sample) as well as adolescent male case-control sample. Consistent with the developments in methodology (viz., genomic control for population heterogeneity [Devlin & Roeder, 1999]), the design of the adolescent component of the study no longer requires recruiting exclusively proband-parents trios. Since, however, it is expected that at least 50% of that sample will consist of full trios, we will have the opportunity to compare the results obtained with both population- and family-based designs.
Aim 2. a) Determine subjects’ haplotypes for each locus using all detected polymorphisms. b) Identify polymorphisms affecting SUD risk using the haplotype data in a measured haplotype analysis.
Aim 3. a) Determine the influence of DNA polymorphisms, both at the level of individual loci and considered jointly as haplotypes, on personality characteristics. b) Evaluate the influence of personality characteristics on the association between the liability to substance dependence and the DNA polymorphisms.
Aim 4. Evaluate the effects of environmental factors (e.g., adverse individual life experiences, affiliation with delinquent peers, high environmental crime) on the variation in liability to substance dependence and its relationship with genetic polymorphisms.
This conceptual model illustrates the hypothesized relationships. Even though the effects of single genes may be small, their attributable risk may be large because of a high frequency of high-risk-associated alleles in the population. Their combined effect may be substantial. Moreover, the effect of drug abuse prevention that could be developed based on the knowledge of genetic mechanisms may be greater than the "natural" contribution of such mechanisms to SD risk variation in the population. The results will allow for more accurate estimation of the risk for SD and suggest approaches for prevention.
Investigators
Michael Vanyukov (PI)
Bernie Devlin
Robert Ferrell
Galina Kirillova
Levent Kirisci
Publications
Related sites
Join this project - help science and earn money!!!
This study recruits 12-18 year old males diagnosed with drug dependence, and their parents.
To enroll, call 412-622-6174. Calls are confidential. The research data are protected by a governmental Certificate of Confidentiality.
Address:
Michael M. Vanyukov, Ph.D.
University of Pittsburgh
707 Salk Hall
Pittsburgh, PA 15261
Fax: (412) 624-1929
E-mail: mmv@pitt.edu
Last revised: August 06, 2002
