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.
Key Words
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Article Info
Publication History
Published online: July 26, 2012
Accepted:
June 6,
2012
Received in revised form:
June 5,
2012
Received:
March 29,
2012
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
