Background
Abnormality of the V-akt murine thymoma viral oncogene homologue 1 (AKT1) may be a
predisposing factor in schizophrenia. Recent evidence supporting this hypothesis showed
decreased AKT1 protein levels in patients with schizophrenia and significant association
of AKT1 haplotypes according to the transmission disequilibrium test.
Methods
We provide the first replication of this evidence using a relatively large case–control
sample (507 Japanese schizophrenia and 437 control subjects). We genotyped five single
nucleotide polymorphisms (SNPs) from the original study and one additional SNP.
Results
We found a positive association with an SNP (SNP5) different from the original study’s
findings (SNP3) and also significance in the haplotypes constructed from the combination
of SNP5. Linkage disequilibrium around SNP5 was complex and may produce this positive
association.
Conclusions
Our study provides support for the theory that AKT1 is a susceptibility gene for Japanese
schizophrenia. Fine linkage disequilibrium mapping is required for a conclusive result.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Pedigree disequilibrium tests for multilocus haplotypes.Genet Epidemiol. 2003; 25: 115-121
- Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia.Nat Genet. 2004; 36: 131-137
- The structure of haplotype blocks in the human genome.Science. 2002; 296: 2225-2229
- The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.Prog Neurobiol. 2001; 65: 391-426
- Phosphatidylinositol 3-kinase.Mol Psychiatry. 2003; 8: 217-224
- Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia.Nat Genet. 2004; 36: 725-731
- Further investigation of linkage disequilibrium SNPs and their ability to identify associated susceptibility loci.Ann Hum Genet. 2004; 68: 240-248
- COX-2 gene promoter haplotypes and prostate cancer risk.Carcinogenesis. 2004; 25: 961-966
- The future of genetic case-control studies.Adv Genet. 2001; 42: 191-212
- Association of a haplotype in the serotonin 5-HT4 receptor gene (HTR4) with Japanese schizophrenia.Am J Med Genet. 2003; 121B: 7-13
- The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease.Am J Hum Genet. 2003; 73: 1438-1443
- Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease.Am J Hum Genet. 2004; 74: 1121-1127
- Assessing the performance of the haplotype block model of linkage disequilibrium.Am J Hum Genet. 2003; 73: 502-515
- Haplotype blocks and linkage disequilibrium in the human genome.Nat Rev Genet. 2003; 4: 587-597
- Control of synaptic strength, a novel function of Akt.Neuron. 2003; 38: 915-928
Article info
Publication history
Published online: October 21, 2004
Accepted:
July 29,
2004
Received in revised form:
July 9,
2004
Received:
April 9,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- ErratumBiological PsychiatryVol. 66Issue 5
- PreviewA labeling error has been discovered in “Association of AKT1 with schizophrenia confirmed in a Japanese population” by Ikeda et al., which appeared in Biological Psychiatry, Volume 56, Number 9 (2004; 56:698–700). Specifically, for rs2494732 (SNP5), the identities of the common and rare frequency nucleotides were inadvertently reversed by the authors, so that G is replaced by A and vice versa.
- Full-Text
- Preview
