Cannabis use and risk of schizophrenia: a Mendelian randomization study

Vaucher, J. et al. (2018) Cannabis use and risk of schizophrenia: a Mendelian randomization study. Molecular Psychiatry, 23(5), pp. 1287-1292. (doi: 10.1038/mp.2016.252) (PMID:28115737) (PMCID:PMC5984096)

Abstract

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known. Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32 330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent. Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09–1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19–1.67; P-value for heterogeneity =0.76). The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09–1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.

• Item Type: Articles
• Additional Information: JV is supported by the Swiss National Science Foundation (P2LAP3_155086). AML is supported by the Swiss National Science Foundation (323530_151479). MVH works in a Unit that receives funds from the University of Oxford and UK Medical Research Council (MRC-E270/4). This research has been conducted using the UK Biobank resource (UK Biobank application reference number 6553) that has been funded by the Wellcome Trust Medical Charity, Medical Research Council, Department of Health of Scottish Government, the Northwest Regional Development Agency, the Welsh Assembly Government and the British Heart Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Daniel and Ward, Dr Joey and Pell, Professor Jill and Sattar, Professor Naveed and Lyall, Dr Donald
• Authors: Vaucher, J., Keating, B.J., Lasserre, A.M., Gan, W., Lyall, D.M., Ward, J., Smith, D.J., Pell, J.P., Sattar, N., Paré, G., and Holmes, M.V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health
• Journal Name: Molecular Psychiatry
• Publisher: Nature Publishing Group
• ISSN: 1359-4184
• ISSN (Online): 1476-5578
• Published Online: 24 January 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Molecular Psychiatry 23(5): 1287-1292
• Publisher Policy: Reproduced under a Creative Commons License