Genetic vulnerability to schizophrenia is associated with cannabis use patterns during adolescence

Abstract

Background: Previously reported comorbidity between schizophrenia and substance use may be explained by shared underlying risk factors, such as genetic background. The aim of the present longitudinal study was to investigate how a genetic predisposition to schizophrenia was associated with patterns of substance use (cannabis use, smoking, alcohol use) during adolescence (comparing ages 13-16 with 16-20 years).

Method: Using piecewise latent growth curve modelling in a longitudinal adolescent cohort (RADAR-Y study, N = 372), we analyzed the association of polygenic risk scores for schizophrenia (PRS; p-value thresholds (p_t) < 5e-8 to p_t < 0.5) with increase in substance use over the years, including stratified analyses for gender. Significance thresholds were set to adjust for multiple testing using Bonferroni at p ≤ 0.001.

Results: High schizophrenia vulnerability was associated with a stronger increase in cannabis use at age 16-20 (PRS thresholds p_t < 5e-5 and p_t < 5e-4; p_t < 5e-6 was marginally significant), whereas more lenient PRS thresholds (PRS thresholds p_t < 5e-3 to p_t < 0.5) showed the reverse association. For smoking and alcohol, no clear relations were found.

Conclusions: In conclusion, our findings support a relation between genetic risk to schizophrenia and prospective cannabis use patterns during adolescence. In contrast, no relation between alcohol and smoking was established.

Keywords: Adolescence; Alcohol use; Cannabis use; Genetic; Polygenic risk score; Schizophrenia; Smoking; Substance use.