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5. GENETIC BASIS OF SUBSTANCE DEPENDENCE




                     common types of genetic studies in humans and the types of information
                     these studies provide are summarized below. Animal studies are also briefly
                     presented.

                     Family, twin and adoption studies: estimations of heritability

                     Family, twin and adoption studies can be used to determine whether or not
                     there is a genetic contribution to psychoactive substance use and
                     dependence, but they do not provide evidence to determine which particular
                     gene is involved. Twin and adoption studies also help to dissociate
                     environmental factors from genetic factors.
                        Family studies examine the inheritance of traits through a family, in order
                     to find out about patterns of inheritance and the relative risk of inheriting a
                     disorder.
                        Twin studies are based on the fact that monozygotic (identical) twins share
                     identical genetic material, while dizygotic (fraternal) twins share the same
                     degree of genetic similarity as non-twin siblings.  Presumably, twins raised
                     together share very similar environments. If genetic effects are present, then
                     monozygotic twins should be more alike, with respect to those effects, than
                     dizygotic twins. This allows an estimation of the genetic contribution to
                     psychoactive substance dependence. These types of studies provide evidence
                     that variation in the vulnerability to substance dependence in populations is
                     influenced by both individual genotypes and environmental differences
                     (Heath et al., 1999a; Vanyukov & Tarter, 2000).
                        Adoption studies are capable of almost completely separating genetic and
                     environmental influences on the variation in the vulnerability to a disorder
                     (except contributions of antenatal and early postnatal environmental factors)
                     (Heath et al., 1999a; Vanyukov & Tarter, 2000); in this way they complement
                     the more traditional twin studies. Using adoption studies, environmental
                     factors can be separated from genetic factors, since children adopted at birth
                     are raised in an environment that is different from that of their genetic family.
                     In this way, environmental factors such as socioeconomic status, learning
                     about substance use, exposure to psychoactive drugs, etc., are randomized.
                     For example, if a particular family shows a high level of substance dependence
                     from generation to generation, it is difficult to know how much of this is
                     attributable to shared genes, and how much is attributable to the shared
                     environment. With adoption studies, the effect of the environment is factored
                     out, and thus, it is easier to determine more clearly the contribution of
                     genetics.

                     Identifying chromosomal locations of interest: linkage studies
                     Twin and adoption studies give an estimation of the proportion of variation
                     in a trait that is due to genetics; however, they do not provide any information
                     about which genes or chromosomes are involved.  Linkage and association


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