The impact of a genome-wide supported psychosis variant in the ZNF804A gene on memory function in schizophrenia

Authors

  • Ryota Hashimoto,

    Corresponding author
    1. Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, Suita, Osaka, Japan
    2. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    3. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
    • Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine, D3, 2-2, Yamadaoka, Suita, Osaka 5650871, Japan.
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  • Kazutaka Ohi,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
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  • Yuka Yasuda,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
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  • Motoyuki Fukumoto,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
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  • Masao Iwase,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Naomi Iike,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
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  • Michiyo Azechi,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Koji Ikezawa,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Masahiko Takaya,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Hidetoshi Takahashi,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Hidenaga Yamamori,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    2. Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Tomo Okochi,

    1. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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  • Hitoshi Tanimukai,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Shinji Tagami,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Takashi Morihara,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Masayasu Okochi,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Toshihisa Tanaka,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Takashi Kudo,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Hiroaki Kazui,

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • Nakao Iwata,

    1. CREST (Core Research for Evolutionary Science and Technology) of JST (Japan Science and Technology Agency), Tokyo, Japan
    2. Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
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  • Masatoshi Takeda

    1. Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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  • How to Cite this Article: Hashimoto R, Ohi K, Yasuda Y, Fukumoto M, Iwase M, Iike N, Azechi M, Ikezawa K, Takaya M, Takahashi H, Yamamori H, Okochi T, Tanimukai H, Tagami S, Morihara T, Okochi M, Tanaka T, Kudo T, Kazui H, Iwata N, Takeda M. 2010. The impact of a genome-wide supported psychosis variant in the ZNF804A gene on memory function in schizophrenia. Am J Med Genet Part B 153B:1459–1464.

Abstract

A recent genome-wide association study showed that a variant (rs1344706) in the ZNF804A gene was associated with schizophrenia and bipolar disorder. Replication studies supported the evidence for association between this variant in the ZNF804A gene and schizophrenia and that this variant is the most likely susceptibility variant. Subsequent functional magnetic resonance imaging studies in healthy subjects demonstrated the association of the high-risk ZNF804A variant with neural activation during a memory task and a theory of mind task. As these cognitive performances are disturbed in patients with schizophrenia, this gene may play a role in cognitive dysfunction in schizophrenia. The aim of the current study was to investigate the potential relationship between this ZNF804A polymorphism and memory function. The effects of the high-risk ZNF804A genotype, diagnosis, and genotype–diagnosis interaction on verbal memory, visual memory (VisM), attention/concentration, and delayed recall (measured by the Wechsler Memory Scale-Revised) were analyzed by two-way analysis of covariance in 113 patients with schizophrenia and 184 healthy subjects. Consistent with previous studies, patients with schizophrenia exhibited poorer performance on all indices as compared to healthy control subjects (P < 0.001). A significant ZNF804A genotype–diagnosis interaction was found for VisM performance (P = 0.0012). Patients with the high-risk T/T genotype scored significantly lower on VisM than G carriers did (P = 0.018). In contrast, there was no genotype effect for any index in the healthy control subjects (P > 0.05). Our data suggest that rs1344706 may be related to memory dysfunction in schizophrenia. © 2010 Wiley-Liss, Inc.

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