To assess to what extent associations between schizophrenia, cannabis use, and cigarette use are due to shared genetics, we investigated the association between schizophrenia genetic risk and longitudinal patterns of adolescent cigarette and cannabis use.

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use (14-19 years) were investigated in up to 3,925 ALSPAC individuals. Mediation models were estimated to assess the mediating effects of a range of cognitive, emotional, and behavioural phenotypes.

It was found that the schizophrenia polygenic score was associated with late-onset cannabis use (OR=1.23; 95% CI=1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, increased emotional difficulties, antisocial behaviour, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting the analyses for genetic liability to cannabis or cigarettes use or using polygenic scores that excluded the CHRNA5-A3-B4 gene cluster, provided consistent evidence that genetic risk for schizophrenia was associated with late-onset adolescent cannabis use.

In conclusion, our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence, and that this is not mediated through the cognitive, emotional, behavioural, or social phenotypes examined in this study.

Funding: This study was supported by MRC (grant number MR/M006727/1) and the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol.
 
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