Austin-Zimmerman, Isabelle and Spinazzola, Edoardo and Quattrone, Diego and Wu-Choi, Beatrice and Trotta, Giulia and Li, Zhikun and Johnson, Emma and Richards, Alexander L and Freeman, Tom P and Tripoli, Giada and Gayer-Anderson, Charlotte and Rodriguez, Victoria and Jongsma, Hannah E and Ferraro, Laura and La Cascia, Caterina and Tosato, Sarah and Tarricone, Ilaria and Berardi, Domenico and Bonora, Elena and Seri, Marco and D'Andrea, Giuseppe and Szöke, Andrei and Arango, Celso and Bobes, Julio and Sanjuán, Julio and Santos, Jose Luis and Arrojo, Manuel and Velthorst, Eva and Bernardo, Miguel and Del-Ben, Cristina Marta and Rossi Menezes, Paulo and Selten, Jean-Paul and Jones, Peter B and Kirkbride, James B and Rutten, Bart P F and Tortelli, Andrea and Llorca, Pierre-Michel and de Haan, Lieuwe and Stilo, Simona and La Barbera, Daniele and Lasalvia, Antonio and Schurnhoff, Franck and Pignon, Baptiste and van Os, Jim and Lynskey, Michael and Morgan, Craig and O' Donovan, Michael and Lewis, Cathryn M and Sham, Pak C and Murray, Robin M and 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, Early online, pp. 1-13. 10.1017/S0033291724002058.
External website: https://www.cambridge.org/core/journals/psychologi...
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, = 3.21 × 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.
A Substance use and dependence > Effects or consequences
B Substances > Cannabis / Marijuana
E Concepts in biomedical areas > Pharmacology and toxicology > Potency / strength
G Health and disease > Disease by cause (Aetiology) > Genetic disorder / epigenetic
G Health and disease > Behavioural and mental health disorder (Psychosis / mood)
VA Geographic area > Europe
VA Geographic area > Europe > United Kingdom
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