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Review
. 2008 Oct 12;363(1507):3213-22.
doi: 10.1098/rstb.2008.0104.

Review. Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders

Chloe C Y Wong  1 , Gunter Schumann
Affiliations
Review

Review. Genetics of addictions: strategies for addressing heterogeneity and polygenicity of substance use disorders

Chloe C Y Wong et al. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Addictions are common psychiatric disorders that exert high cost to the individual and to society. Addictions are a result of the interplay of multiple genetic and environmental factors. They are characterized by phenotypic and genetic heterogeneity as well as polygenicity, implying a contribution of different neurobiological mechanisms to the clinical diagnosis. Therefore, treatments for most substance use disorders are often only partially effective, with a substantial proportion of patients failing to respond. To address heterogeneity and polygenicity, strategies have been developed to identify more homogeneous subgroups of patients and to characterize genes contributing to their phenotype. These include genetic linkage and association studies as well as functional genetic analysis using endophenotypes and animal behavioural experimentation. Applying these strategies in a translational context aims at improving therapeutic response by the identification of subgroups of addiction patients for individualized, targeted treatment strategies. This article aims to discuss strategies addressing heterogeneity and polygenicity of substance use disorders by presenting results of recent research on genetic and environmental components of addiction. It will also introduce the European IMAGEN study that aims to integrate methodical approaches discussed in order to identify the genetic and neurobiological basis of behavioural traits relevant to the development of addictions.

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Figures

Figure 1
Figure 1
Relationship between phenotypic heterogeneity, genetic heterogeneity and polygenicity in alcohol use disorders.
Figure 2
Figure 2
Relationship between endophenotypes, disease (phenotype) and aetiological factors including genes, environment and gene–environment interaction. A1 and A2 represent, respectively, the alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) polymorphisms that are associated with reduced alcohol consumption in the southern Asian population. A3 represents the association of CHRM2 with low amplitude of P300 event-related potential (ERP). An, additive genetic factors; A×E, gene–environment interaction; E1–m, environmental factors.
Figure 3
Figure 3
Neurotransmitter systems and environmental factors that have been associated with alcohol use disorders.
See this image and copyright information in PMC

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MeSH terms

Substances