TY - JOUR
T1 - 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
AU - EU-GEI WP2 Group
AU - Austin-Zimmerman, Isabelle
AU - Spinazzola, Edoardo
AU - Quattrone, Diego
AU - Wu-Choi, Beatrice
AU - Trotta, Giulia
AU - Li, Zhikun
AU - Johnson, Emma
AU - Richards, Alexander L.
AU - Freeman, Tom P.
AU - Tripoli, Giada
AU - Gayer-Anderson, Charlotte
AU - Rodriguez, Victoria
AU - Jongsma, Hannah E.
AU - Ferraro, Laura
AU - La Cascia, Caterina
AU - Tosato, Sarah
AU - Tarricone, Ilaria
AU - Berardi, Domenico
AU - Bonora, Elena
AU - Seri, Marco
AU - D’Andrea, Giuseppe
AU - Szöke, Andrei
AU - Arango, Celso
AU - Bobes, Julio
AU - Sanjuán, Julio
AU - Santos, Jose Luis
AU - Arrojo, Manuel
AU - Velthorst, Eva
AU - Bernardo, Miguel
AU - Del-Ben, Cristina Marta
AU - Menezes, Paulo Rossi
AU - Selten, Jean Paul
AU - Jones, Peter B.
AU - Kirkbride, James B.
AU - Rutten, Bart P.F.
AU - Tortelli, Andrea
AU - Llorca, Pierre Michel
AU - de Haan, Lieuwe
AU - Stilo, Simona
AU - La Barbera, Daniele
AU - Lasalvia, Antonio
AU - Schurnhoff, Franck
AU - Pignon, Baptiste
AU - van Os, Jim
AU - Lynskey, Michael
AU - Morgan, Craig
AU - O’ Donovan, Michael
AU - Lewis, Cathryn M.
AU - Sham, Pak C.
AU - Murray, Robin M.
AU - Vassos, Evangelos
AU - Di Forti, Marta
N1 - Publisher Copyright:
© The Author(s), 2024.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - cannabis
KW - first-episode psychosis
KW - high-potency cannabis
KW - polygenic risk score
KW - psychosis
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85211754279&partnerID=8YFLogxK
U2 - 10.1017/S0033291724002058
DO - 10.1017/S0033291724002058
M3 - Article
C2 - 39637925
AN - SCOPUS:85211754279
SN - 0033-2917
JO - Psychological medicine
JF - Psychological medicine
ER -