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

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 natur...

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Main Authors: Vaucher, J, Keating, B, Lasserre, A, Gan, W, Lyall, D, Ward, J, Smith, D, Pell, J, Sattar, N, Paré, G, Holmes, M
Format: Journal article
Language:English
Published: Nature Publishing Group 2017
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author Vaucher, J
Keating, B
Lasserre, A
Gan, W
Lyall, D
Ward, J
Smith, D
Pell, J
Sattar, N
Paré, G
Holmes, M
author_facet Vaucher, J
Keating, B
Lasserre, A
Gan, W
Lyall, D
Ward, J
Smith, D
Pell, J
Sattar, N
Paré, G
Holmes, M
author_sort Vaucher, J
collection OXFORD
description 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.
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spelling oxford-uuid:b6368ab8-7f1b-4907-9a81-e77f5056e3382022-03-27T04:39:19ZCannabis use and risk of schizophrenia: a Mendelian randomization study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b6368ab8-7f1b-4907-9a81-e77f5056e338EnglishSymplectic Elements at OxfordNature Publishing Group2017Vaucher, JKeating, BLasserre, AGan, WLyall, DWard, JSmith, DPell, JSattar, NParé, GHolmes, MCannabis 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.
spellingShingle Vaucher, J
Keating, B
Lasserre, A
Gan, W
Lyall, D
Ward, J
Smith, D
Pell, J
Sattar, N
Paré, G
Holmes, M
Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title_full Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title_fullStr Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title_full_unstemmed Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title_short Cannabis use and risk of schizophrenia: a Mendelian randomization study.
title_sort cannabis use and risk of schizophrenia a mendelian randomization study
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