Association study of PDE4B gene variants in scandinavian schizophrenia and bipolar disorder multicenter case–control samples

Authors

  • Anna K. Kähler,

    Corresponding author
    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Medical Genetics, Oslo University Hospital – Ulleval, Oslo, Norway
    3. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
    • Section for Psychosis Research, Building 49, Department for Research and Development, Division of Psychiatry, Oslo University Hospital – Ulleval, Kirkeveien 166, N-0407 Oslo, Norway.
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  • Mona K. Otnæss,

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
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  • Katrine V. Wirgenes,

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
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  • Thomas Hansen,

    1. Research Institute of Biological Psychiatry, H:S Sct. Hans Hospital, Roskilde, Denmark
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  • Erik G. Jönsson,

    1. Department of Clinical Neuroscience, HUBIN Project, Psychiatry Section, Karolinska Institutet and Hospital, Stockholm, Sweden
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  • Ingrid Agartz,

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Clinical Neuroscience, HUBIN Project, Psychiatry Section, Karolinska Institutet and Hospital, Stockholm, Sweden
    3. Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
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  • Håkan Hall,

    1. Department of Clinical Neuroscience, HUBIN Project, Psychiatry Section, Karolinska Institutet and Hospital, Stockholm, Sweden
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  • Thomas Werge,

    1. Research Institute of Biological Psychiatry, H:S Sct. Hans Hospital, Roskilde, Denmark
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  • Gunnar Morken,

    1. Østmarka Psychiatric Department, St Olavs Hospital and Institute of Neuroscience, Norwegian University of Technology and Science, Trondheim, Norway
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  • Ole Mors,

    1. Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
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  • Erling Mellerup,

    1. Center of Psychiatry, Rigshospitalet, Copenhagen, Denmark
    2. Department of Neuroscience and Pharmacology, University of Copenhagen, Laboratory of Neuroscience, Copenhagen, Denmark
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  • Henrik Dam,

    1. Center of Psychiatry, Rigshospitalet, Copenhagen, Denmark
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  • Pernille Koefod,

    1. Center of Psychiatry, Rigshospitalet, Copenhagen, Denmark
    2. Department of Neuroscience and Pharmacology, University of Copenhagen, Laboratory of Neuroscience, Copenhagen, Denmark
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  • Ingrid Melle,

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
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  • Vidar M. Steen,

    1. Dr. Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway
    2. Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
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  • Ole A. Andreassen,

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
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  • Srdjan Djurovic

    1. Institute of Psychiatry, University of Oslo, Oslo, Norway
    2. Department of Medical Genetics, Oslo University Hospital – Ulleval, Oslo, Norway
    3. Department of Psychiatry, Oslo University Hospital – Ulleval, Oslo, Norway
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  • How to Cite this Article: Kähler AK, Otnæss MK, Wirgenes KV, Hansen T, Jönsson EG, Agartz I, Hall H, Werge T, Morken G, Mors O, Mellerup E, Dam H, Koefod P, Melle I, Steen VM, Andreassen OA, Djurovic S. 2010. Association Study of PDE4B Gene Variants in Scandinavian Schizophrenia and Bipolar Disorder Multicenter Case–Control Samples. Am J Med Genet Part B 153B:86–96.

Abstract

The phosphodiesterase 4B (PDE4B), which is involved in cognitive function in animal models, is a candidate susceptibility gene for schizophrenia (SZ) and bipolar disorder (BP). Variations in PDE4B have previously been associated with SZ, with a suggested gender-specific effect. We have genotyped and analyzed 40 and 72 tagging single nucleotide polymorphisms (tagSNPs) in SZ and BP multicenter samples, respectively, from the Scandinavian Collaboration on Psychiatric Etiology (SCOPE), involving 837 SZ cases and 1,473 controls plus 594 BP cases and 1,421 partly overlapping controls. Six and 16 tagSNPs were nominally associated (0.0005 ≤ P ≤ 0.05) with SZ and BP, respectively, in the combined samples or in gender-specific subgroups. None of these findings remained significant after correction for multiple testing. However, a number of tagSNPs found to be nominally associated with SZ and BP were located in a high LD region spanning the splice site of PDE4B3, an isoform with altered brain expression in BP patients. Four tagSNPs were associated with SZ in women, but none in men, in agreement with the previously reported gender-specific effect. Proxies of two nominally associated SNPs in the SZ sample were also associated with BP, but the genotypic effect (i.e., homozygosity for the minor allele), pointed in opposite directions. Finally, four SNPs were found to be associated with Positive And Negative Syndrome Scale (PANSS) positive symptom scores in a subgroup of SZ patients (n = 153) or SZ female patients (n = 70). Further studies are needed to evaluate the implicated PDE4B region of interest, for potential involvement in SZ and BP susceptibility. © 2009 Wiley-Liss, Inc.

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