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Meta-Analysis
. 2018 Feb 14;13(2):e0192658.
doi: 10.1371/journal.pone.0192658. eCollection 2018.

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis

Thomas Stephanus Johannes Vaessen  1 , Lea de Jong  1 , Annika Theresia Schäfer  1 , Thomas Damen  1 , Aniek Uittenboogaard  1 , Pauline Krolinski  1 , Chinyere Vicky Nwosu  1 , Florentina Maria Egidius Pinckaers  1 , Iris Leah Marije Rotee  1 , Antonius Petrus Wilhelmus Smeets  1 , Ayşegül Ermiş  2 , James L Kennedy  3 , Dorien H Nieman  4 , Arun Tiwari  3 , Jim van Os  5   6   7 , Marjan Drukker  5
Affiliations
Meta-Analysis

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis

Thomas Stephanus Johannes Vaessen et al. PLoS One. .

Abstract

Background: Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive.

Objective: A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met).

Data sources: PubMed, Embase, PsychInfo.

Study eligibility criteria: All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome.

Study appraisal and synthesis methods: A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions".

Results: For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16-0.08).

Limitation: A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects.

Conclusion: The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram.
Fig 2
Fig 2. Forest plot case-only studies (figure shows odds ratios; random effects).
Fig 3
Fig 3. Funnel plot case-only studies.
Fig 4
Fig 4. Forest plot dichotomous outcomes (figure shows regression coefficient of the interaction term, random effects).
Fig 5
Fig 5. Forest plot continuous outcomes (figure shows regression coefficient of the interaction term, random effects).
See this image and copyright information in PMC

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