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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
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Genetics of Substance Use Disorders.
1Department of Psychiatry, University of Washington, Box 356560, Seattle, WA 98195, USA.
Summary
Genetic factors significantly influence substance use disorders, particularly alcohol and nicotine dependence. While some gene variants offer protection, most genetic risks for substance abuse remain unknown, highlighting the need for advanced genomic research.
Area of Science:
- Genetics and Genomics
- Neuroscience
- Pharmacology
Background:
- Substance abuse disorders (SUDs) exhibit a substantial genetic predisposition.
- Known genetic risk factors for alcohol abuse involve alcohol-metabolizing enzymes and GABA-A receptors.
- Specific gene mutations (ADH1B, ALDH2) confer protection against alcohol dependence.
Purpose of the Study:
- To review the genetic underpinnings of substance abuse disorders.
- To identify known genetic associations for alcohol and nicotine use disorders.
- To highlight the gaps in understanding genetic vulnerability for other illicit drug use.
Main Methods:
- Review of existing literature on genetic factors in substance abuse.
- Analysis of common variants and functional mutations in relevant genes.
- Identification of chromosomal regions and specific genes implicated in SUDs.
Main Results:
- Common variants in alcohol-metabolizing enzymes and GABA-A receptors are linked to alcohol abuse risk.
- Protective functional missense mutations in ADH1B and ALDH2 identified.
- Polymorphisms in nicotinic acetylcholine receptors (chromosome 15q24) and CYP2A6 mutations associated with nicotine use disorders.
Conclusions:
- Genetic factors play a critical role in the susceptibility to substance abuse disorders.
- Significant genetic contributions to alcohol and nicotine dependence are understood, but risks for other drugs are less clear.
- Advanced whole-genome sequencing is crucial for elucidating the remaining unexplained genetic vulnerability in SUDs.
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