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5. GENETIC BASIS OF SUBSTANCE DEPENDENCE

CHAPTER 5

Genetic Basis of Substance Dependence

Introduction
The aim of this chapter is to critically assess the evidence for a genetic
contribution to the risk of developing psychoactive substance use and
dependence in humans. While individual genetic differences contribute to
the development of substance dependence, genetic factors are but one
contributor to the complex interplay of physiological, social, cultural and
personal factors that are involved. A list of commonly used genetic terms is
provided in Box 5.1.
The classical (and popular) view of human genetics is one in which genetic
mutation is the direct and usually only cause of a particular illness, for
example, the single gene – or Mendelian – disorders such as Huntington’s
disease. Single gene diseases are caused by a specific mutated gene, and the
mutation is both necessary and sufficient to cause the illness. Unlike single
gene disorders, which are rare and might affect 1 in 10 000 people, complex
disorders, such as substance dependence, are common in the population,
often affecting 1 in 100 or more people. Complex disorders are clearly not
caused by genes alone, but by the interaction between genes and the
environment. Thus exposure to psychoactive substances could have a much
greater effect on somebody who carries a genetic vulnerability to substance
dependence, than on someone who does not.
Genetic vulnerability, or predisposition, to substance dependence is likely
to be tied to several distinct genes (or multiple alleles), each producing a
small effect, which might increase risk of developing substance dependence
by 2–3 fold. Any one of the genes on its own will be insufficient to cause
dependence, but several different genes may all contribute to the
vulnerability. It is hypothesised that not everyone who carries a “risk gene”
for substance use or dependence will become dependent, and likewise some
of those who become dependent will not carry that particular genetic risk
factor. It is the combination of the presence of several distinct genes or alleles
which may be important, rather than a single gene. These genetic
contributions to vulnerability seem likely to be distributed over several
distinct regions (loci) on the chromosomes.
This chapter will address the genetics of substance use disorders in general,
but will also specifically examine the data for opioid, alcohol and tobacco
dependence, as these substances have received a substantial amount of

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