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

Norton, Nadine, Williams, Hywel J., Dwyer, Sarah, Carroll, Liam, Peirce, Tim, Escott-Price, Valentina ORCID:, Segurado, Ricardo, Nikolov, Ivan, Williams, Nigel Melville ORCID:, Ikeda, Masashi, Iwata, Nakao, Owen, Michael John ORCID: and O'Donovan, Michael Conlon ORCID: 2007. Association analysis of AKT1 and schizophrenia in a UK case control sample. Schizophrenia Research 93 (1-3) , pp. 58-65. 10.1016/j.schres.2007.02.006

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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 r(2)=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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0920-9964
Last Modified: 17 Nov 2022 13:23

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