|(C;C)||2.1||greater odds of cannabis-associated psychosis|
|(C;T)||1.5||slightly greater risk of temporary paranoia when toking (pot)|
|(T;T)||1||lower odds of psychosis|
rs2494732 is a SNP in the AKT1 gene, encoding one of three serine/threonine-protein kinases regulating numerous processes such as cell survival, growth and angiogenesis. Medical conditions that may be linked to the rarer (minor) rs2494732(C) allele include drug response, schizophrenia, and drug-related psychoses, in particular, cannabis-related psychosis.
[PMID 26882038] A study of 442 healthy, once-a-month cannabis users between the ages of 16-23 to see if AKT1 variants influenced acute psychosis response concluded that the number of rs2494732(C) alleles predicted (p = 0.015) acute (i.e. temporary) psychotic response to cannabis. Basically, the more copies someone had of this SNP, the more likely they were to have mind-altering symptoms while stoned. Other factors studied, including gender, ethnicity, and years of cannabis use, did not predict whether they would have these (transient) symptoms. Note that this side-effect (psychosis or paranoia) was infrequent in an absolute sense regardless of genotype.
[PMID 22831980] A case-control study of 489 first-episode psychosis patients concluded that while rs2494732 was not associated with an increased risk of a psychotic disorder, with lifetime cannabis use, or with frequency of use, there was a significant association between psychosis and cannabis use. rs2494732(C;C) individuals with a history of cannabis use had an increased likelihood of a psychotic disorder (odds ratio 2.18, CI: 1.1 - 4.3) when compared with users who were (T;T) carriers. The interaction between the rs2494732 genotype and frequency of use was also somewhat significant (likelihood ratio = 13.39; p = .010). Among daily users, (C;C) carriers had a 7x increase in the odds of psychosis compared with (T;T) carriers (odds ratio 7.23, CI: 1.37 - 38.12).
[PMID 18855532] among (likely Japanese) 120 first-episode neuroleptic-naive schizophrenics treated with risperidone genotyped for 30 variants in misc. dopamine and serotonin (receptors and otherwise) two SNPs in DRD2 (rs1799989 and rs1800497) and two SNPs in AKT1 (rs3803300 and rs2494732) were significant predictors of treatment response to risperidone
The ancestral allele is C in the dbSNP database.
[PMID 22277669] Genetic overlap between schizophrenia and bipolar disorder: A study with AKT1 gene variants and clinical phenotypes
[PMID 16260726] Detection of functional single-nucleotide polymorphisms that affect apoptosis.
[PMID 16395129] Absence of significant associations between four AKT1 SNP markers and schizophrenia in the Taiwanese population.
[PMID 17464696] AKT1 and neurocognition in schizophrenia.
[PMID 18497887] Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans.
[PMID 18715757] Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.
[PMID 19051289] Association of AKT1 with verbal learning, verbal memory, and regional cortical gray matter density in twins.
[PMID 19461960] Absence of AKT1 mutations in glioblastoma.
[PMID 19931325] No association between AKT1 polymorphism and schizophrenia: a case-control study in a Korean population and a meta-analysis.
[PMID 20046382] AKT1 Gene Polymorphisms and Obstetric Complications in the Patients with Schizophrenia.
[PMID 21041608] Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up.
[PMID 21775978] AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder.
[PMID 21842521] AKT1 polymorphisms and survival of early stage non-small cell lung cancer.
[PMID 22150081] The AKT1 gene is associated with attention and brain morphology in schizophrenia.
[PMID 23747160] No association between AKT1 gene variants and schizophrenia: a Malaysian case-control study and meta-analysis
[PMID 25060489] Genetic variants in AKT1 gene were associated with risk and survival of OSCC in Chinese Han Population
[PMID 25184405] Subclinical psychotic experiences in healthy young adults: associations with stress and genetic predisposition
[PMID 27305091] Genetic Association of TCF4 and AKT1 Gene Variants with the Age at Onset of Schizophrenia.