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

Austin-Zimmerman, Isabelle, Spinazzola, Edoardo, Quattrone, Diego, Wu-Choi, Beatrice, Trotta, Giulia, Li, Zhikun, Johnson, Emma, Richards, Alexander L., Freeman, Tom P., Tripoli, Giada, Gayer-Anderson, Charlotte, Rodriguez, Victoria, Jongsma, Hannah E., Ferraro, Laura, La Cascia, Caterina, Tosato, Sarah, Tarricone, Ilaria, Berardi, Domenico, Bonora, Elena, Seri, Marco, D'Andrea, Giuseppe, Szöke, Andrei, Arango, Celso, Bobes, Julio, Sanjuán, Julio, Santos, Jose Luis, Arrojo, Manuel, Velthorst, Eva, Bernardo, Miguel, Del-Ben, Cristina Marta, Rossi Menezes, Paulo, Selten, Jean-Paul, Jones, Peter B., Kirkbride, James B., Rutten, Bart P. F., Tortelli, Andrea, Llorca, Pierre-Michel, de Haan, Lieuwe, Stilo, Simona, La Barbera, Daniele, Lasalvia, Antonio, Schurnhoff, Franck, Pignon, Baptiste, van Os, Jim, Lynskey, Michael, Morgan, Craig, O'Donovan, Michael ORCID: https://orcid.org/0000-0001-7073-2379, Lewis, Cathryn M., Sham, Pak C., Murray, Robin M., Vassos, Evangelos and Di Forti, Marta 2024. 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. Psychological Medicine 10.1017/S0033291724002058

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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. 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. 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. 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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	Cambridge University Press
ISSN:	0033-2917
Date of First Compliant Deposit:	13 December 2024
Date of Acceptance:	2 August 2024
Last Modified:	16 Dec 2024 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/174721

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