Molecular Genetics of Substance Abuse Vulnerability: Remarkable Recent Convergence of Genome Scan Results

Authors

  • GEORGE R. UHL

    Corresponding author
    1. Molecular Neurobiology Branch, National Institute on Drug Abuse—International Research Program, National Institutes of Health, Box 5180, Baltimore, Maryland 21224, USA
      Address for correspondence: George R. Uhl, M.D., Ph.D., Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180, Baltimore, MD 21224. Voice: 410-550-2843 ext. 146; fax: 410-550-1535. guhl@intra.nida.nih.gov
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Address for correspondence: George R. Uhl, M.D., Ph.D., Molecular Neurobiology Branch, NIDA-IRP, NIH, Box 5180, Baltimore, MD 21224. Voice: 410-550-2843 ext. 146; fax: 410-550-1535. guhl@intra.nida.nih.gov

Abstract

Abstract: Classical genetic studies document strong complex genetic contributions to abuse of multiple addictive substances. Goals of molecular genetic studies of addiction include: (1) locating chromosomal regions that contain allelic gene variants that contribute to vulnerability to drug dependence and (2) discovering which alleles of which gene markers and which genes provide these enhanced vulnerabilities. Genome scanning provides an approach to these goals. Until recently, data from genome scanning studies did not convincingly identify chromosomal positions for allelic variants predisposing to substance dependence. Nominal results of initial genome scans for alcohol and nicotine dependence failed to display much agreement; no two studies’ results seemed to identify the same chromosomal regions for addiction vulnerability alleles. However, recent data from our association-based genome scans for illegal addictions, reanalyses of prior linkage-based results, and data from even newer linkage-based genome scans now provide a striking body of converging results. Sixteen chromosomal regions are identified by reproducible positive results obtained in multiple populations. These 16 regions are thus good candidates to harbor common allelic variants that confer human vulnerability to addiction to several classes of substances. Genomic markers that identify allelic variants that reproducibly alter addiction vulnerability in studies in several populations provide powerful tools for clinical research in addictions and addiction treatments.

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