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

Jones, Hannah J, Hammerton, Gemma, McCloud, Tayla, Hines, Lindsey A., Wright, Caroline, Gage, Suzanne H., Holmans, Peter, Jones, Peter B., Smith, George Davey, Linden, David E. J., O'Donovan, Michael C., Owen, Michael J., Walters, James T., Munafò, Marcus R., Heron, Jon and Zammit, Stanley 2020. Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence. Psychological Medicine 10.1017/S0033291720001798
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Abstract

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 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 use 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 behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Publisher: Cambridge University Press (CUP)
ISSN: 0033-2917
Date of First Compliant Deposit: 21 May 2020
Date of Acceptance: 15 May 2020
Last Modified: 31 Jul 2020 15:52
URI: http://orca.cf.ac.uk/id/eprint/131845

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