The Mechanisms Underlying the Intergenerational Transmission of Substance Use and Misuse: An Integrated Research Approach

Substance use and substance use disorders run in families. While it has long been recognized that the etiology of substance use behaviors and disorders involves a combination of genetic and environmental factors, two key questions remain largely unanswered: (1) the intergenerational transmission through which these genetic predispositions are passed from parents to children, and (2) the molecular mechanisms linking genetic variants to substance use behaviors and disorders. This article aims to provide a comprehensive conceptual framework and methodological approach for investigating the intergenerational transmission of substance use behaviors and disorders, by integrating genetic nurture analysis, gene expression imputation, and weighted gene co-expression network analysis. We also additionally describe two longitudinal cohorts - the Brisbane Longitudinal Twin Study in Australia and the Lifelines Cohort Study in the Netherlands. By applying the methodological framework to these two unique datasets, our future research will explore the complex interplay between genetic factors, gene expression, and environmental influences on substance use behaviors and disorders across different life stages and populations.