Academic journal article Alcohol Research

The Genetics of Alcohol and Other Drug Dependence

Academic journal article Alcohol Research

The Genetics of Alcohol and Other Drug Dependence

Article excerpt

Alcohol dependence and dependence on other drugs frequently co-occur, and strong evidence suggests that both disorders are, at least in part, influenced by genetic factors. Indeed, studies using twins suggest that the overlap between dependence on alcohol and on other drugs largely results from shared genetic factors. This common genetic liability, which also extends to antisocial behavior, has been conceptualized as a general predisposition toward a variety of forms of psychopathology characterized by disinhibited behavior (i.e., externalizing psychopathology). Accordingly, many of the genetic factors affecting risk for dependence on alcohol or other drugs appear to act through a general externalizing factor; however, other genetic factors appear to be specific to a certain disorder. In recent years, researchers have identified numerous genes as affecting risk for dependence on alcohol and other drugs. These include genes involved in alcohol metabolism as well as in the transmission of nerve cell signals and modulation of nerve cell activity (i.e., γ-aminobutyric acid [GABA] and acetylcholinergic neurotransmission and the endogenous opioid and cannabinoid systems). KEY WORDS: Alcohol and other drug (AOD) dependence (AODD); co-morbid AOD dependence; genetics and heredity; genetic theory of AODD; genetic risk factors; AODR genetic markers

This article explores the hypothesis that certain genetic factors increase a person's risk of both alcohol abuse and dependence and other drug abuse and dependence. It first reviews the evidence suggesting that certain genetic factors contribute to the development of alcohol and other drug (AOD) use disorders, as well as to the development of a variety of forms of externalizing psychopathology- that is, psychiatric disorders char-acterized by disinhibited behavior, such as antisocial personality disorder, atten-tion deficit/hyperactivity disorder, and conduct disorder. After summarizing the difficulties associated with, and recent progress made in, the identification of specific genes associated with AOD dependence, the article then dis-cusses evidence that implicates several genes in a person's risk for dependence on both alcohol and illicit drugs.

GENETIC EPIDEMIOLOGY OF AOD DEPENDENCE

Alcohol dependence frequently co- occurs with dependence on illicit drugs (Hasin et al. 2007). Both alco-hol use disorders (i.e., alcohol abuse and alcohol dependence) and drug use disorders (drug abuse and drug dependence) are influenced by several factors. For example, family, twin, and adoption studies1 have convincingly demonstrated that genes con-tribute to the development of alcohol dependence, with heritability estimates ranging from 50 to 60 percent for both men and women (McGue 1999). Dependence on illicit drugs only more recently has been investi-gated in twin samples, but several studies now suggest that illicit drug abuse and dependence also are under significant genetic influence. In these studies of adult samples, heritability estimates ranged from 45 to 79 per-cent (for reviews, see Agrawal and Lynskey 2006; Kendler et al. 2003a; Tsuang et al. 2001).

Twin studies also can be used to assess the extent to which the cooccurrence of disorders is influenced by genetic and/or environmental factors. Thus, a finding that the cor-relation between alcohol dependence in twin 1 and drug dependence in twin 2 is higher for identical (i.e.,monozygotic) twins, who share 100 percent of their genes, than for fraternal (i.e., dizygotic) twins, who share on average only 50 percent of their genes, indicates that shared genes influence the risk of both alcohol and drug dependence. The twin studies conducted to date support the role of such shared genetic factors. For example, in the largest twin study of the factors underlying psychiatric disorders, Kendler and colleagues (2003b) analyzed data from the Virginia Twin Registry and found that a common genetic factor contributed to the total variance in alcohol dependence, illicit drug abuse and dependence, conduct disorder, and adult antisocial behavior. …

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