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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

understanding the complex human processes of dependence through careful
application of complex genetic approaches.
The two main approaches to estimate genetic and environmental
components of phenotypic variance are twin and adoption studies. Twin
studies strongly indicate the presence of genetic risk factors for multiple
aspects of smoking and alcohol dependence, including initiation,
continuation, amount consumed and cessation. Moreover a plethora of
studies indicate considerable commonality between tobacco and alcohol
dependence, making the identification of both common and substance-
unique genetic influences crucial and challenging. In addition to estimating
genetic liability, these studies provide further information about
environmental contributions, identifying that which is shared (i.e. that which
both twins have in common and which contributes to their similarity) and
that which is non-shared (contributing to the relative dissimilarity) (Heath,
Madden & Martin, 1998; Vanyukov & Tarter, 2000; Jacob et al., 2001).

Table 5.1 Summary of heritability of dependence on selected substances

Substance Heritability Linkage Candidate genes
estimates
(%)
Nicotine 60–80 Chromosome 5q near D1 CYP2A6
receptor loci Dopamine D4 receptor
Dopamine Beta hydroxylase
Alcohol 52–63 Loci on chromosomes 4q, ALDH2
6, 1, 7, 2, 11p, 10q ADH
CYP2E1
GABA α6, β1, β3, γ2
A
Dopamine D4 receptor
COMT (catechol-O
methyltransferase)
Serotonin 2A receptor
Opioids 70 None identified CYP2D6
Combined risk for 50–80 Loci on chromosome 15, Dopamine D1 receptor
substance 19q12-13 Dopamine D2 receptor
dependence Dopamine D4 receptor
in general Monoamine oxidase A

References
Agarwal DP (2001) Genetic polymorphisms of alcohol metabolizing enzymes.
Pathology and Biology (Paris), 49:703–709.
Albanese V et al. (2001) Quantitative effects on gene silencing by allelic variation
at a tetranucleotide microsatellite. Human Molecular Genetics, 10:1785–1792.

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