Genetic and environmental risk factors for illicit substance use and use disorders: Joint analysis of self and co-twin ratings

Abstract

The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.

Fig. 1

Squares represent observed variables and circles represent latent variables. Colors denote different parts of the model. Black measurement model; grey random measurement error; yellow systematic measurement error; dark red common additive genetic effects; dark green (Color figure online)

Fig. 2

A bivariate twin model for selfreport and co-twin report. This model was used to find out whether the same genetic (denoted by the letter A), shared environmental (C), and unique environmental risk factors (E) influence self and co-twin report. The model contains two set of factors: those that are common for self and co-twin report (in red denoted by subscript s), and those that are unique to co-twin report (in grey denoted by u). We did not assume self and co-twin report to be equally reliable measures of illicit substance use, so the loadings of the common factors were allowed to differ (denoted by a ‘prime’ symbol) (Color figure online)

Fig. 3

a Best-fit model for liability to lifetime use of five illicit substances by 1,791 male twins from a population based registry. Black circles represent latent factors of phenotypic liability, and squares represent observed liability to illicit substance use—all which have a variance of unity. The path coefficients represent standardized regression coefficient. The square of the product of coefficients from the upstream variables to the downstream variables is the explained variance in observed illicit substance use. b Best-fit model for liability to lifetime use disorder of cannabis, cocaine, and stimulants by 1,791 male twins from a population based registry. Black circles represent latent factors of phenotypic liability, and squares represent observed liability to illicit substance use—all which have a variance of unity. The path coefficients represent standardized regression coefficient. The square of the product of coefficients from the upstream variables to the downstream variables is the explained variance in observed illicit substance use

Fig. 4. Sources of phenotypic correlation predicted by best fit model for lifetime use disorders of thee classes of illicit substances