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

Published online by Cambridge University Press:  09 June 2020

Hannah J. Jones Open the ORCID record for Hannah J. Jones [Opens in a new window] ,
Gemma Hammerton ,
Tayla McCloud ,
Lindsey A. Hines ,
Caroline Wright ,
Suzanne H. Gage ,
Peter Holmans ,
Peter B Jones ,
George Davey Smith  and
David E. J. Linden
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Hannah J. Jones*
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
Gemma Hammerton
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
Tayla McCloud
Affiliation:
Division of Psychiatry, University College London, London, UK
Lindsey A. Hines
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK
Caroline Wright
Affiliation:
Population Health Sciences, Bristol Medical School, University of Bristol, UK
Suzanne H. Gage
Affiliation:
Department of Psychological Sciences, University of Liverpool, Liverpool, UK
Peter Holmans
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Peter B Jones
Affiliation:
Department of Psychiatry, University of Cambridge, Cambridge, UK
George Davey Smith
Affiliation:
Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
David E. J. Linden
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Michael C. O'Donovan
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Michael J. Owen
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
James T. Walters
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Marcus R. Munafò
Affiliation:
Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, UK
Jon Heron
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
Stanley Zammit
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
*
Author for correspondence: Hannah J. Jones, E-mail: hannah.jones@bristol.ac.uk
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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.

Keywords

ALSPACcannabis-usecigarette-usemediationpolygenic scoreschizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 1 , January 2022 , pp. 132 - 139
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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