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Journal article

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

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.Molecular Psychiatry advance online publication, 24 January 2017; doi:10.1038/mp.2016.252.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/mp.2016.252

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Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
OCDEM
Role:
Author



Publisher:
Nature Publishing Group
Journal:
Molecular Psychiatry More from this journal
Publication date:
2017-01-01
Acceptance date:
2016-11-28
DOI:
EISSN:
1476-5578
ISSN:
1359-4184


Language:
English
Keywords:
Pubs id:
pubs:673349
UUID:
uuid:b6368ab8-7f1b-4907-9a81-e77f5056e338
Local pid:
pubs:673349
Source identifiers:
673349
Deposit date:
2017-04-12

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