Genetic risk for schizophrenia influences substance use in emerging adulthood : an event-level polygenic prediction model

Background: Emerging adulthood is a peak period of risk for alcohol and illicit drug use, as well as psychiatric disorders. Recent advances in statistical genetics suggest that the co-occurrence of these phenomena is due, in part, to a shared genetic etiology. Here, we examined how genetic risk for schizophrenia influenced trajectories of five substance use behaviors as they occurred in daily life across emerging adulthood. Method: Non-Hispanic European participants provided DNA samples and completed daily reports of alcohol and drug use for one month per year across four years (N=28,372 unique observations of N=318 participants). A two-level hierarchical linear model was then used to analyze the relationships between genetic risk for schizophrenia, participant age, and the five substance use phenotypes. Results: The present study yields two major insights. First, results indicated that genetic risk for schizophrenia predicted emerging adults’ overall likelihood to engage in illicit drug use and polysubstance use (concurrent illicit drug use and alcohol use or binge drinking), but did not predict alcohol use-only phenotypes. Second, the present findings indicated that genetic variants related to schizophrenia predicted the rate of age-related change in substance use. Conclusions: The present study used a novel combination of polygenic prediction and repeated phenotyping to characterize the influence of genetic risk for schizophrenia on patterns of age-related change in substance use across emerging adulthood. Results suggest that genes implicated in schizophrenia exert both broad and developmentally-specific influences on substance use behaviors in healthy individuals.