Follow-up analysis supported AKT1 rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis.
Follow-up analysis supported AKT1rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis.
The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder.
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.
Association of Single Nucleotide Polymorphisms in Catechol-O-Methyltransferase and Serine-Threonine Protein Kinase Genes in the Pakistani Schizophrenic Population: A Study with Special Emphasis on Cannabis and Smokeless Tobacco.
These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.
Moreover, AKT1 risk alleles may increase the incidence of cannabis use in patients with a psychotic disorder, but AKT1 does not appear to mediate the effect of cannabis on BMI.