Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users
Open accessAbstract
Background Cannabis use is associated with an increased risk of psychosis. One study has suggested that genetic variation in the AKT1 gene might influence this effect.Methods In a case-control study of 489 first-episode psychosis patients and 278 control subjects, we investigated the interaction between variation at the AKT1 rs2494732 single nucleotide polymorphism and cannabis use in increasing the risk of psychosis.Results The rs2494732 locus was not associated with an increased risk of a psychotic disorder, with lifetime cannabis use, or with frequency of use. We did, however, find that the effect of lifetime cannabis use on risk of psychosis was significantly influenced by the rs2494732 locus (likelihood ratio statistic for the interaction = 8.54; p = .014). Carriers of the C/C genotype with a history of cannabis use showed a greater than twofold increased likelihood of a psychotic disorder (odds ratio = 2.18 [95% confidence interval: 1.12, 4.31]) when compared with users who were T/T carriers. Moreover, the interaction between the rs2494732 genotype and frequency of use was also significant at the 5% level (likelihood ratio = 13.39; p = .010). Among daily users, C/C carriers demonstrated a sevenfold increase in the odds of psychosis compared with T/T carriers (odds ratio = 7.23 [95% confidence interval: 1.37, 38.12]).Conclusions Our findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users.
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More recently an interaction has been reported, and replicated in one study, between cannabis use and AKT1 on psychosis risk.
“More recently an interaction has been reported (39), and replicated in one study, between cannabis use and AKT1 on psychosis risk (40); however there are substantial concerns around gene environment interaction studies (38,41), and currently evidence that effects of cannabis differ according to variation at AKT1 is not robust.”
From Association Between Cannabis and Psychosis: Epidemiologic Evidence (2016) · cites this paper as [40]
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- Authors
- Di Forti, M., Iyegbe, C., Sallis, H., Kolliakou, A., Falcone, M. A., Paparelli, A., Sirianni, M., La Cascia, C., Stilo, S. A., Marques, T. R., Handley, R., Mondelli, V., Dazzan, P., Pariante, C., David, A. S., Morgan, C., Powell, J., & Murray, R. M.
- Affiliations
- King's College London (GB)
- Magna Graecia University (IT)
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2012-11
- Volume
- 72
- Issue
- 10
- Pages
- 811-816
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2007497521
- Cited by
- 234
- References
- 36
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 19 · 2021: 11 · 2020: 19 · 2019: 18 · 2018: 17 · 2017: 28 · 2016: 25 · 2015: 29 · 2014: 27 · 2013: 19 · 2012: 3
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Psychiatry Research Trust
- Seventh Framework Programme (HEALTH-F2-2009-241909)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- AKT1, single nucleotide polymorphisms, cannabis use, psychosis risk, first-episode psychosis, gene-environment interaction, daily cannabis use, genetic susceptibility
- MeSH terms
- Adult, Marijuana Abuse, Demography, Female, Genetic Testing, Humans, London, Male, Psychotic Disorders, Risk Factors, Socioeconomic Factors, Confidence Intervals, Odds Ratio, Case-Control Studies, Episode of Care, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, International Classification of Diseases, Proto-Oncogene Proteins c-akt, Gene-Environment Interaction
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