Confirmation that the AKT1 (rs2494732) Genotype Influences the Risk of Psychosis in Cannabis Users


      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.


      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.


      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]).


      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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      Linked Article

      • Progress in Gene Environment Studies
        Biological PsychiatryVol. 72Issue 10
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          After a wave of candidate gene studies claiming positive associations with psychiatric disorders, a period of disappointing negative findings and meta-analysis followed (1). This led to fierce debate as to how the field as a whole could have condoned the publication of so many false-positive findings. Genome-wide studies were subsequently favored because these unbiased approaches were expected to have a higher probability of producing true-positive, replicable results. Because of the need for extremely large studies, the genome-wide studies have led to unprecedented global collaborations that have yielded true progress, identifying several genes and pathways that can illuminate the etiology of psychiatric disorders.
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