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.
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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, EU-GEI WP2 Group, O' Donovan Michael, Lewis Cathryn M, Sham Pak C, Murray Robin M, Vassos Evangelos, Di Forti Marta
Аннотация
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.