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Study Description

Our principal goal was to determine the chromosomal locations of genetic variations associated with increased vulnerability to heroin dependence. This goal was attained by identifying specific DNA markers that are genetically linked to heroin dependence. We collected blood and diagnostic information (using a structured diagnostic interview) from 1230 people (sib-pairs) having DSM-IV defined heroin dependence as well as from their parents and other affected and unaffected siblings, when possible. Genotype and clinical data was archived using database software. We conducted a multipoint linkage analysis using the guidelines of Lander and Kruglyak to assert statistical significance, and followed up on regions of interest with a dense set of markers to evaluate candidate genes.

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Study Inclusion/Exclusion Criteria

The minimum pedigree ascertained consists of affected sibling pairs (ASP) and two parents who provided a blood sample. We excluded ASPs if both parents have heroin dependence. When two parents are available, the unaffected siblings were not needed for the linkage analyses of DSM-IV defined heroin dependence. We also collected unaffected siblings. In cases in which it was impossible to obtain genotypic data on both parents, unaffected sibs were useful for establishing identity by state. Our preference was for families in which both parents can provide DNA. However, families with one available parent and at least two unaffected siblings, in addition to the affected sib-pair, were included.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Targeted Genotyping BioRealm Smokescreen Genotyping Array N/A N/A
Study History

Although the available data strongly suggest that a substantial component of the etiology of drug dependence is mediated by gene expression in the central nervous system, a detailed understanding of the involved mechanisms has remained elusive. Genetic studies have not been able to determine the mode of inheritance. The main goal of the proposed program of research was to detect one or more genes responsible for the genetic transmission of heroin dependence. We selected heroin dependence, because previous research has demonstrated that heroin is the most "heritable" form of illicit drug dependence, and that heroin has the greatest degree of genetic variance which is not shared with other drugs. Research has adduced evidence for familial specificity of heroin abuse. Our principal goal was to determine the chromosomal locations of genetic variations associated with increased vulnerability to heroin dependence by identifying specific DNA markers that are genetically linked to heroin dependence.

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Study Attribution
  • Principal Investigator
    • Ming Tsuang MD, PhD, DSc. University of California, San Diego, CA, USA.
  • Funding Source
    • R01DA012846. National Institutes of Health, Bethesda, MD, USA.