Molecular Genetics of Addiction

Ming D Li, University of Virginia, Virginia, USA

Published online: May 2010

DOI: 10.1002/9780470015902.a0022425

Addictions to both licit and illicit drugs are common chronic brain disorders that are extremely costly to the individuals and society. Although genetics contributes significantly to vulnerability to these affective disorders, the susceptibility genes underlying them are largely unknown. Recent genome-wide linkage and association studies have implicated several common genomic regions and genes in the aetiology of addiction to multiple substances. For example, variants in the 2 subunit of gamma-aminobytric acid type A (GABAA) receptor have been found repeatedly in association with alcoholism and alcohol-related phenotypes. Recently, a cluster on chromosome 15q24/q25.1 that encompasses the genes for nicotine acetylcholine receptor subunits 5, 3 and 4 was implicated in addiction to tobacco and other substances as well. Current efforts aim not only to replicate these findings in independent samples, but also to determine the functional mechanisms of these associations.

Key Concepts:

  • Drug addiction is a chronic brain disorder.
  • Both human and animals studies reveal that addiction is determined not only by genetic and environmental factors, but also by their interactions.
  • Significant genetic overlaps exist among addictions to different substances.
  • It is important to determine not only genetic but also environmental factors involved in the aetiology of addictions.
  • Several genomic regions have been revealed to harbour susceptibility genes for multiple addictive disorders.
  • Genes such as those encoding GABAA and GABAB receptor subunits, neurexins 1 and 2, and some nicotinic receptor subunits are associated with addictions.
  • Determination of gene–environmental interactions is as important and challenging as determining gene–gene interactions.
  • Small microRNAs may play important roles in the mediation of expression of genes implicated in addictions.

Keywords: genetics; addiction; dependence; alcohol; smoking; opioid; interaction

Figure 1. A summary of chromosomal locations of nominated peaks or intervals for addictions to alcohol, cannabis, cocaine, heroin, nicotine and their related phenotypes with ‘significant’ or ‘suggestive’ evidence of linkage by independent studies based on at least two substances of abuse. The determination of ‘significant’ or ‘suggestive’ evidence of linkage at each linkage peak was based on the rigorous criteria proposed by Lander and Kruglyak (1995), which defines an LOD of >3.6 or a P-value of <2.2×10–5 as a ‘significant linkage’ and an LOD of >2.2 but <3.6 or a P-value of 7.4×10–4 as a ‘suggestive’ linkage. Each linkage is given either with a colour-filled circle or a triangle representing a reported linkage peak or region, respectively. Each colour represents a type of abused substance that could come from the same or different reports/studies. The ‘units’ for each chromosome is ‘cM’. Partial contents of this figure have been reported in Li and Burmeister (2009). Reprinted with permission from Nature Publishing Group.
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Related Sub-Topics:

Neurobiology of Disease | Learning and Memory: Cellular and Molecular Mechanisms | Neural Networks and Behaviour | Postsynaptic Signalling Mechanisms | Molecular Genetics of Common and Complex Disease | Linkage Analysis | Epigenetics and Disease
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Article Title: Molecular Genetics of Addiction
 
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Li, Ming D(May 2010) Molecular Genetics of Addiction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022425]