Genetic and Environmental Connections Shared between Transmissible Liability to Substance Use Disorder and Substance Use Initiation

In the absence of face-valid indicators, particularly in children, liability to substance use/addiction requires quantification. The Transmissible Liability Index (TLI) was developed for this purpose by employing a high-risk design and item response theory and quantifies this liability in childhood, before substance exposure. Because the TLI places liability to substance use disorder on a common scale, it can also facilitate harmonization across datasets collected from different populations. This study extends prior research by examining genetic and environmental contributions to TLI and its relationship with liability to the initiation of licit and illicit substance use. The study utilizes data of TLI, and substance use tracked from age 11 to age 25 from longitudinal twin studies in Virginia and Minnesota. Results showed that TLI is highly heritable and that substance use initiation (SUI) reflected a mixture of genetic and shared environmental influences varying across substance classes, consistent with the principle that initiation is more environmentally sensitive than progression. The genetic correlations between childhood TLI and lifetime SUI are consistently stronger than the environmental correlations and support a developmental interpretation in which early heritable liability manifests in SUI and, further downstream, in disorder. In addition to confirming TLI’s high heritability, predictive validity, and utility for dataset harmonization, it supports the feasibility of identifying high- and average-resistance samples, to be used for selecting specific indicators of resistance to substance use/addiction.