Specificity of Genetic and Environmental Risk Factors for Use and Abuse/Dependence of Cannabis, Cocaine, Hallucinogens, Sedatives, Stimulants, and Opiates in Male Twins

Abstract

In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.

Familial transmission of derived phenotypes for molecular genetic studies of substance use disorders

“…Nonetheless, our finding is consistent with twin data suggesting that most drug use disorders share a common genetic diathesis (Kendler, et al, 2003, Tsuang, et al, 1998. If that is true, it seems reasonable to posit that members of SUD families share an underlying trait that may be indexed by psychopathological or associated cognitive features.…”

“…This idea is consistent with two bodies of evidence. First, many forms of substance use have been shown through twin and family studies to share genetic risk factors with several forms of psychopathology (Compton, et al, 2005, Kendler, et al, 2003. Second, two twin studies have shown that, although individual SUDs may have some unique sources of genetic etiology, much of the genetic susceptibility to SUDs can be explained by a common genetic diathesis (Kendler, et al, 2003, Tsuang, et al, 1998.…”

“…First, many forms of substance use have been shown through twin and family studies to share genetic risk factors with several forms of psychopathology (Compton, et al, 2005, Kendler, et al, 2003. Second, two twin studies have shown that, although individual SUDs may have some unique sources of genetic etiology, much of the genetic susceptibility to SUDs can be explained by a common genetic diathesis (Kendler, et al, 2003, Tsuang, et al, 1998. Taken together, these findings suggest that the genetic predisposition to SUDs may be indexed by clinical features external to the diagnosis of SUDs, which are typically associated with psychopathology such as symptoms and evidence of adaptive and cognitive impairments.…”

Linkage scan for quantitative traits identifies new regions of interest for substance dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample

“…In adults, genetic factors contribute to 40-60% of the total variance in risk for alcohol dependence (Dick et al, 2006;Heath et al, 1997;Kendler et al, 1994;Prescott et al, 1995;Tsuang et al, 2001), while for illegal drug dependence, estimates of heritability range from 35-75% (Kendler et al, 2003a;Lynskey et al, 2002;Tsuang et al, 1996;Tsuang et al, 2001;van den Bree et al, 1998). Results from multivariate twin analyses suggest that (i) the liability for dependence on various illicit drug classes is governed, in part, by common genetic factors (Kendler et al, 2003a;Tsuang et al, 1998), and (ii) a significant proportion of the genetic influences on alcohol and illicit drug dependence may be overlapping (Bierut et al, 1998;Kendler et al, 2003b;McGue et al, 2000;Tsuang et al, 2001). …”

Evidence for a two-stage model of dependence using the NESARC and its implications for genetic association studies

“…While twin studies assessing conditional dependence support the two-stage model of dependence (initiation as distinct from dependence), some aspects of these studies leave the issue unresolved, especially for illicit substances: (a) studies typically had limited statistical power to assess specific drugs types (Kendler et al, 1999), or (b) focused on whether risk factors were common or unique across substances when the two stages (initiation and dependence) were considered separately (e.g., Kendler et al, 2003), or (c) did not focus on illicit substances, but rather, alcohol and tobacco (e.g., Heath et al, 1990;Kendler et al, 1999;Madden et al, 1999;Maes et al, 2004;True et al, 1999;Vink et al, 2006). Further, some authors have suggested that the previous twin studies provided only indirect evidence on progression to dependence (Neale et al, 2006), with newer methods only recently introduced to directly address conjoint shared and unique influences on the different stages in twin studies (Agrawal et al, 2005;Neale et al, 2006).…”