| Title: | The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies |
| Journal: | Psychological Medicine |
| Published: | 1 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39637925/ |
| DOI: | https://doi.org/10.1017/s0033291724002058 |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/fea08b1b-38d2-484b-8034-9a1b8586f860 |
Publication 14218
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Abstract
BACKGROUND: The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.</p>
METHODS: Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.</p>
RESULTS: In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08-8.43, p = 3.21 × 10-10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.</p>
CONCLUSIONS: Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.</p>
53 Authors
- Isabelle Austin-Zimmerman
- Edoardo Spinazzola
- Diego Quattrone
- Beatrice Wu-Choi
- Giulia Trotta
- Zhikun Li
- Emma Johnson
- Alexander L. Richards
- Tom P. Freeman
- Giada Tripoli
- Charlotte Gayer-Anderson
- Victoria Rodriguez
- Hannah E. Jongsma
- Laura Ferraro
- Caterina La Cascia
- Sarah Tosato
- Ilaria Tarricone
- Domenico Berardi
- Elena Bonora
- Marco Seri
- Giuseppe D'Andrea
- Andrei Szöke
- Celso Arango
- Julio Bobes
- Julio Sanjuán
- Jose Luis Santos
- Manuel Arrojo
- Eva Velthorst
- Miguel Bernardo
- Cristina Marta Del-Ben
- Paulo Rossi Menezes
- Jean-Paul Selten
- Peter B. Jones
- James B. Kirkbride
- Bart P. F. Rutten
- Andrea Tortelli
- Pierre-Michel Llorca
- Lieuwe de Haan
- Simona Stilo
- Daniele La Barbera
- Antonio Lasalvia
- Franck Schurnhoff
- Baptiste Pignon
- Jim van Os
- Michael Lynskey
- Craig Morgan
- EU-GEI WP2 Group
- Michael O' Donovan
- Cathryn M. Lewis
- Pak C. Sham
- Robin M. Murray
- Evangelos Vassos
- Marta Di Forti
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