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RESEARCH PRODUCT
Confirmation that the AKT1 (rs2494732) genotype influences the risk of psychosis in cannabis users.
John PowellAnna KolliakouCarmine M. ParianteMiriam SirianniCraig MorganAlessandra Paparelli La Cascia CaterinaConrad IyegbeTiago Reis MarquesMarta Di FortiPaola DazzanM. Aurora FalconeAnthony S. DavidRobin M. MurrayValeria MondelliRowena HandleySimona A. StiloHannah M Sallissubject
AdultMalemedicine.medical_specialtyPsychosisMarijuana AbuseEpisode of CarePolymorphism Single NucleotideRisk AssessmentOddsInternational Classification of DiseasesRisk FactorsLondonSettore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat.medicineConfidence IntervalsOdds RatioHumansGenetic Predisposition to DiseaseGenetic TestingGene–environment interactionPsychiatrySettore MED/25 - PsichiatriaBiological PsychiatryDemographybiologyCase-control studyOdds ratiomedicine.diseasebiology.organism_classificationConfidence intervalPsychotic DisordersSocioeconomic FactorsCase-Control StudiesFemaleGene-Environment InteractionAKT1 gene cannabis use gene environment interaction psychosis schizophrenia signaling pathwaysCannabisRisk assessmentPsychologyProto-Oncogene Proteins c-aktDemographydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-11-01 | Biological psychiatry |