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Chapter 2. Genetics of Addiction

Joel Gelernter, M.D.; Henry R. Kranzler, M.D.
DOI: 10.1176/appi.books.9781585623440.344402

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Excerpt

Like other important psychiatric traits, substance dependence (SD) is genetically influenced, and this genetic influence is complex. This means that the genetic influence plays out in something other than a Mendelian mode (i.e., dominant, recessive, or X-linked), and, practically speaking, this means there are many genes involved—none of which ever fully determines that a person will be affected. Moreover, as with other complex traits, SD risk is influenced by both genetic and environmental factors. But in the case of SD risk there is a special twist: there is a necessary component of gene-by-environment interaction. A person cannot become substance dependent without exposure to the substance, regardless of genetic constitution. This places a trait like cocaine dependence (you cannot be cocaine dependent if you do not have access to cocaine) in contrast to a trait like schizophrenia, in which, as far as we know, special environmental exposure is not required for the condition to develop.

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Table Reference Number

The major forms of substance dependence (alcohol, nicotine, opioid, and cocaine dependence, for example) are all heritable.

Genes that influence heritable traits may be identified. Linkage studies point to chromosomal locations; association studies, and other methods of analysis that make use of linkage disequilibrium relationships, point to specific genes.

Replicable gene–phenotype relationships have been identified for many kinds of substance dependence.

The best-known, and best-replicated, findings so far in substance dependence genetics involve alcohol metabolism genes. Polymorphic variation in numerous genes that encode enzymes important for alcohol metabolism influences risk for alcohol dependence.

Lately, methodological progress in genetics has been extremely rapid. New methodologies that make it possible to acquire orders-of-magnitude more genetic information than was possible even a few years ago all but guarantee an enhanced pace for progress in the future.

Gene-by-environment interaction is an important area of research in psychiatric genetics. Recently, examples of such interaction have been demonstrated for substance dependence genetics.

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Four types of substance dependence are among the greatest public health problems in the United States. Which of the following is not one of these four?
2.
Familial and genetic factors are important for the development of alcohol dependence, as established by twin, family, and adoption studies. The largest twin studies have yielded heritability estimates in which range?
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There are currently two general methods that can be used to identify risk genes without a prior knowledge of risk mechanisms. One of these is called a genomewide association study. Which of the following statements is descriptive of this approach?
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