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

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Hammerton, Gemma 
McCloud, Tayla 
Hines, Lindsey A 
Wright, Caroline 


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.



ALSPAC, cannabis-use, cigarette-use, mediation, polygenic score, schizophrenia, Schizophrenia, Cannabis, Nicotiana, Longitudinal Studies, Genetic Predisposition to Disease, Risk Factors, Tobacco Products

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Psychol Med

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Cambridge University Press (CUP)


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Medical Research Council (MR/M006727/1)
The UK Medical Research Council (MRC) and Wellcome (grant number 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website. Measures used were specifically funded by the MRC (grant number G0800612/86812) and the Wellcome Trust (grant numbers 076467/Z/05/Z, 086684, 092731). GWAS data were generated by Sample Logistics and Genotyping Facilities at the Wellcome Trust Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This study was supported by MRC (grant number MR/M006727/1) and the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol National Health Service Foundation Trust and the University of Bristol. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research or the Department of Health. HJJ, GH and MRM are members of the Medical Research Council Integrative Epidemiology Unit at the University of Bristol funded by the MRC (grant numbers MC_UU_00011/1, MC_UU_00011/7). GH is funded by a Sir Henry Wellcome Postdoctoral Fellowship (grant number 209138/Z/17/Z). CW is funded by a Cancer Research UK Population Research Postdoctoral Fellowship (grant number C60153/A23895).