Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Hannah J Jones*, Gemma L Hammerton, Tayla McCloud, Lindsey A Hines, Caroline L Wright, Suzie H Gage, P Holmans, Peter Jones, George Davey Smith, D E Linden, Michael C O'Donovan, Michael John Owen, James T Walters, Marcus R Munafo, Jon E Heron, Stanley Zammit

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)


Background: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We therefore examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence, and mediating pathways for any association to inform potential reduction strategies.

Methods: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 years to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

Results: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p-threshold of 0.05, was associated with late-onset cannabis use (OR=1.23; 95% CI=1.08,1.41), but not with cigarette or early-onset cannabis classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p-threshold, provided results consistent with our main analyses.

Conclusions: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioural phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Original languageEnglish
JournalPsychological Medicine
Publication statusAccepted/In press - 15 May 2020

Structured keywords

  • polygenic score
  • cigarette-use
  • cannabis-use
  • schizophrenia
  • mediation
  • Physical and Mental Health
  • Tobacco and Alcohol

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  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.


    Project: Research

    Rework of IEU Munafo Programme

    Munafo, M. R.


    Project: Research

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