title: Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users.
abstract: 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.
authors: Department of Psychosis Studies, Institute of Psychiatry, Kings College London, London, United Kingdom. marta.diforti@kcl.ac.uk
authors: Marta
authors: M
authors: Di Forti
authors: Conrad
authors: C
authors: Iyegbe
authors: Hannah
authors: H
authors: Sallis
authors: Anna
authors: A
authors: Kolliakou
authors: M Aurora
authors: MA
authors: Falcone
authors: Alessandra
authors: A
authors: Paparelli
authors: Miriam
authors: M
authors: Sirianni
authors: Caterina
authors: C
authors: La Cascia
authors: Simona A
authors: SA
authors: Stilo
authors: Tiago Reis
authors: TR
authors: Marques
authors: Rowena
authors: R
authors: Handley
authors: Valeria
authors: V
authors: Mondelli
authors: Paola
authors: P
authors: Dazzan
authors: Carmine
authors: C
authors: Pariante
authors: Anthony S
authors: AS
authors: David
authors: Craig
authors: C
authors: Morgan
authors: John
authors: J
authors: Powell
authors: Robin M
authors: RM
authors: Murray
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016001:Confidence Intervals; D003710:Demography; D017050:Episode of Care; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D038801:International Classification of Diseases; D008131:London; D008297:Male; D002189:Marijuana Abuse / Q000150:complications / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011618:Psychotic Disorders / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012959:Socioeconomic Factors
chemical_list: D051057:Proto-Oncogene Proteins c-akt