Association analysis of AKT1 and schizophrenia in a UK case control sample

Nadine Norton, Hywel J. Williams, Sarah Dwyer, Liam Carroll, Tim Peirce, Valentina Moskvina, Ricardo Segurado, Ivan Nikolov, Nigel M. Williams, Masashi Ikeda, Nakao Iwata, Michael J. Owen, Michael C. O'Donovan

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Abstract

AKT1 (V-akt murine thyoma viral oncogene homolog 1) is involved in intracellular signalling pathways postulated as of aetiological importance in schizophrenia. Markers in the AKT1 gene have also recently been associated with schizophrenia in two samples of European origin and in Japanese and Iranian samples. Aiming to replicate these findings, we examined ten SNPs spanning AKT1 in a UK case-control sample (schizophrenia cases n = 673, controls n = 716). These included all SNPs previously reported to be associated in European, Japanese and Iranian samples, alone or in haplotypes, as well as additional markers defined by the Haploview Tagger program (pair-wise tagging, minimum r2 = 0.8, minor allele frequency = 0.02). We found no association with single markers (min p = 0.17). We found weak evidence for association (p = 0.04) with a four marker haplotype reported as significant in the original positive European sample of Emamian et al. [Emamian, E.S., Hall, D., Birnbaum, M.J., Karayiorgou, M., Gogos, J.A., 2004. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat. Genet. 36, 131-137] and also an overlapping three marker haplotype (p = 0.016) that had previously been reported as significant in a Japanese sample. Nominal p-values for these haplotypes did not survive correction for multiple testing. Our study provides at best weak support for the hypothesis that AKT1 is a susceptibility gene for schizophrenia. Examination of our own data and those of other groups leads us to conclude that overall, the evidence for association of AKT1 as a susceptibility gene for schizophrenia is weakly positive, but not yet convincing.

Original languageEnglish
Pages (from-to)58-65
Number of pages8
JournalSchizophrenia Research
Volume93
Issue number1-3
DOIs
Publication statusPublished - 01-07-2007

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Schizophrenia
Haplotypes
Single Nucleotide Polymorphism
Genes
Viverridae
Oncogenes
Gene Frequency

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Norton, N., Williams, H. J., Dwyer, S., Carroll, L., Peirce, T., Moskvina, V., ... O'Donovan, M. C. (2007). Association analysis of AKT1 and schizophrenia in a UK case control sample. Schizophrenia Research, 93(1-3), 58-65. https://doi.org/10.1016/j.schres.2007.02.006
Norton, Nadine ; Williams, Hywel J. ; Dwyer, Sarah ; Carroll, Liam ; Peirce, Tim ; Moskvina, Valentina ; Segurado, Ricardo ; Nikolov, Ivan ; Williams, Nigel M. ; Ikeda, Masashi ; Iwata, Nakao ; Owen, Michael J. ; O'Donovan, Michael C. / Association analysis of AKT1 and schizophrenia in a UK case control sample. In: Schizophrenia Research. 2007 ; Vol. 93, No. 1-3. pp. 58-65.
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Norton, N, Williams, HJ, Dwyer, S, Carroll, L, Peirce, T, Moskvina, V, Segurado, R, Nikolov, I, Williams, NM, Ikeda, M, Iwata, N, Owen, MJ & O'Donovan, MC 2007, 'Association analysis of AKT1 and schizophrenia in a UK case control sample', Schizophrenia Research, vol. 93, no. 1-3, pp. 58-65. https://doi.org/10.1016/j.schres.2007.02.006

Association analysis of AKT1 and schizophrenia in a UK case control sample. / Norton, Nadine; Williams, Hywel J.; Dwyer, Sarah; Carroll, Liam; Peirce, Tim; Moskvina, Valentina; Segurado, Ricardo; Nikolov, Ivan; Williams, Nigel M.; Ikeda, Masashi; Iwata, Nakao; Owen, Michael J.; O'Donovan, Michael C.

In: Schizophrenia Research, Vol. 93, No. 1-3, 01.07.2007, p. 58-65.

Research output: Contribution to journalArticle

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AU - Norton, Nadine

AU - Williams, Hywel J.

AU - Dwyer, Sarah

AU - Carroll, Liam

AU - Peirce, Tim

AU - Moskvina, Valentina

AU - Segurado, Ricardo

AU - Nikolov, Ivan

AU - Williams, Nigel M.

AU - Ikeda, Masashi

AU - Iwata, Nakao

AU - Owen, Michael J.

AU - O'Donovan, Michael C.

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Norton N, Williams HJ, Dwyer S, Carroll L, Peirce T, Moskvina V et al. Association analysis of AKT1 and schizophrenia in a UK case control sample. Schizophrenia Research. 2007 Jul 1;93(1-3):58-65. https://doi.org/10.1016/j.schres.2007.02.006