Genetic Studies of Alcoholism and Substance Dependence

Abstract

During the past year, there has been a surge in genetic studies of alcohol and substance dependence. This increased interest is the result both of high repeated-heritability estimates of the addictive disorders and related phenotypes (typically ∼50%-60%) and of the appreciation that methods for detecting, mapping, and characterizing oligogenic susceptibility genes are rapidly improving. Thus, the full promise of genetics may become available to increase prevention and to improve the treatment of these extremely destructive common disorders. This article is primarily a review of recent human linkage and candidate-gene studies of alcoholism and related phenotypes, although we include other forms of substance dependence that show substantial comorbidity with alcoholism and with each other. We do not consider the large body of research that uses animal models to approach these questions.

Genetic polymorphisms in folate and alcohol metabolism and breast cancer risk: a case–control study in Thai women

“…Likewise, the number of striatal dopamine D2 receptors is less in alcohol-preferring humans than in healthy control subjects. The A1 polymorphism of DRD2 TaqI A loci has been considered as a risk factor for alcohol dependence [31,32], but the association between alcoholism and the DRD2 gene remains equivocal in many studies [33][34][35]. In our study, an The propensity for severe drinking has been also hypothesized to be regulated by differential expression of serotonin transporter gene SLC6A4 [36].…”

Linkage Disequilibrium and the Search for Complex Disease Genes

“…Case-control studies can be confounded by population stratification, and there are several empirical examples of this problem (Knowler et al 1988;Reich et al 1999). LD analysis is no exception to this difficulty, and various strategies have been devised to control for stratification.…”

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

“…It is well established that phenotypic variation in the liability to addiction is strongly influenced by differences in individual genotypes and by their interactions with different environmental conditions (Reich et al, 1999;Vanyukov and Tarter, 2000;Uhl et al, 2002). Genetic factors also influence personality traits and temperament clusters, including disinhibition/impulsivity and sensation/novelty seeking which, in turn, have been identified as vulnerability factors for substance use disorders (Bardo et al, 1996;Ebstein et al, 2000;Verheul and van den Brink, 2000;Helmus et al, 2001).…”