Cannabis use and risk of schizophrenia: a Mendelian randomization study.

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State: Public
Version: Final published version
Serval ID
serval:BIB_C3949076B505
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cannabis use and risk of schizophrenia: a Mendelian randomization study.
Journal
Molecular psychiatry
Author(s)
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., Holmes M.V.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
05/2018
Peer-reviewed
Oui
Volume
23
Number
5
Pages
1287-1292
Language
english
Notes
Publication types: Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Adult, Cannabis/metabolism, Case-Control Studies, European Continental Ancestry Group/genetics, Female, Genetic Variation, Humans, Male, Marijuana Abuse/genetics, Marijuana Abuse/psychology, Marijuana Smoking/adverse effects, Marijuana Smoking/genetics, Marijuana Smoking/psychology, Middle Aged, Polymorphism, Single Nucleotide, Random Allocation, Risk Factors, Schizophrenia/etiology, Schizophrenia/genetics, Smokers/psychology
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2017 17:10
Last modification date
20/08/2019 16:38
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