Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users

Marta Di Forti, Conrad Iyegbe, Hannah Sallis, Anna Kolliakou, M Aurora Falcone, Alessandra Paparelli, Miriam Sirianni, Caterina La Cascia, Simona A Stilo, Tiago Reis Marques, Rowena Handley, Valeria Mondelli, Paola Dazzan, Carmine Pariante, Anthony S David, Craig Morgan, John Powell, Robin M Murray

Research output: Contribution to journalArticle (Academic Journal)peer-review

159 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)811-6
Number of pages6
JournalBiological Psychiatry
Issue number10
Publication statusPublished - 15 Nov 2012

Bibliographical note

Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.


  • Adult
  • Case-Control Studies
  • Confidence Intervals
  • Demography
  • Episode of Care
  • Female
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • International Classification of Diseases
  • London
  • Male
  • Marijuana Abuse
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-akt
  • Psychotic Disorders
  • Risk Assessment
  • Risk Factors
  • Socioeconomic Factors

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