Genetic etiology of the common liability to drug dependence: evidence of common and specific mechanisms for DSM-IV dependence symptoms

Abstract

Background: We investigated the etiological nature of comorbid alcohol, tobacco, and cannabis DSM-IV dependence symptoms in late adolescence and young adulthood while accounting for gender differences in the magnitude of genetic and environmental influences.

Methods: Univariate and multivariate twin modeling was used to determine the heritability of each substance and the etiology of multiple drug problems in a sample of 2484 registrants of the Center for Antisocial Drug Dependence who provided data at the second wave of an ongoing longitudinal study. We report on mean and prevalence levels of whole-life DSM-IV dependence symptoms that were assessed with the Composite International Diagnostic Interview-Substance Abuse Module. Biometrical analyses were limited to age-adjusted DSM-IV dependence symptom counts from a subset of twins that reported using alcohol, tobacco, or cannabis in their lifetime.

Results: Male and female alcohol, tobacco, and cannabis DSM-IV symptoms are indicators of a heritable unidimensional latent continuous trait. Additive genetic factors explain more than 60% of the common liability to drug dependence. A larger proportion of the variation in each substance is attributable to substance-specific genetic and environmental factors.

Conclusions: These data suggest that both common and substance-specific genetic and environmental factors contribute to individual differences in the levels of DSM-IV alcohol, tobacco, and cannabis dependence symptoms.

Figure 1. Multivariate biometrical models; Only Twin 1 depicted

Note: Path diagrams of multivariate behavioral genetic models used to describe multivariate or longitudinal data. Figure 1a describes the Independent Pathway Model that consists of a common genetic and environmental factor that describes the covariance between substances, while the specific factors capture genetic and environmental influences that are unique to each substance. The Common Pathway Model, depicted in Figure 1b, is a restricted form of the Independent Pathway Model created by positing that the covariation between substances arises from a latent factor (referred to as Substance Dependence Vulnerability). Abbreviations: A – additive genetic effects; C – shared environmental effects; Common – identifies the portion of the model which estimates factor loadings common to all phenotypes; E – non-shared environmental effects; Specific – describes the portion of the model that identifies genetic or environmental effects that are unique to a particular phenotype, beyond that which may already be shared; Alc – Alcohol; Tob – Tobacco; Can - Cannabis.

Figure 1. Multivariate biometrical models; Only Twin 1 depicted

Note: Path diagrams of multivariate behavioral genetic models used to describe multivariate or longitudinal data. Figure 1a describes the Independent Pathway Model that consists of a common genetic and environmental factor that describes the covariance between substances, while the specific factors capture genetic and environmental influences that are unique to each substance. The Common Pathway Model, depicted in Figure 1b, is a restricted form of the Independent Pathway Model created by positing that the covariation between substances arises from a latent factor (referred to as Substance Dependence Vulnerability). Abbreviations: A – additive genetic effects; C – shared environmental effects; Common – identifies the portion of the model which estimates factor loadings common to all phenotypes; E – non-shared environmental effects; Specific – describes the portion of the model that identifies genetic or environmental effects that are unique to a particular phenotype, beyond that which may already be shared; Alc – Alcohol; Tob – Tobacco; Can - Cannabis.