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Support for involvement of glutamate decarboxylase 1 and neuropeptide y in anxiety susceptibility

Authors

  • Jonas Donner,

    1. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
    3. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
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  • Tessa Sipilä,

    1. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
    3. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
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  • Samuli Ripatti,

    1. Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland
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  • Laura Kananen,

    1. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
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  • Xiangning Chen,

    1. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Kenneth S. Kendler,

    1. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Jouko Lönnqvist,

    1. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
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  • Sami Pirkola,

    1. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
    3. Department of Psychiatry, University of Oulu and Lapland Hospital District, Oulu, Finland
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  • John M. Hettema,

    1. Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia
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  • Iiris Hovatta

    Corresponding author
    1. Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    2. Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
    3. Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
    • Research Program of Molecular Neurology, Biomedicum Helsinki, PO Box 63, FIN-00014, Finland.
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  • How to Cite this Article: Donner J, Sipilä T, Ripatti S, Kananen L, Chen X, Kendler KS, Lönnqvist J, Pirkola S, Hettema JM, Hovatta I. 2012. Support for Involvement of Glutamate Decarboxylase 1 and Neuropeptide Y in Anxiety Susceptibility. Am J Med Genet Part B 159B:316–327.

  • Conflict of interest: none.

Abstract

Genetic mapping efforts have identified putative susceptibility genes for human anxiety disorders. The most intensively studied genes are involved in neurotransmitter metabolism and signaling or stress response. In addition, neuropeptides and targets of anxiolytics have been examined. It has become apparent that gene × environment interactions may explain individual variation in stress resilience and predisposition to mental disorders. We aimed to replicate previous genetic findings in 16 putative anxiety susceptibility genes and further test whether they modulate the risk for developing an anxiety disorder in adulthood after childhood stress exposure. We tested 93 single-nucleotide polymorphisms (SNPs) for genetic association to anxiety disorders in the Finnish population-based Health 2000 sample (282 cases and 575 matched controls). In addition, we examined by logistic regression modeling whether the SNP genotypes modified the effect of the number of self-reported childhood adversities on anxiety disorder risk. The most significant evidence for association was observed in glutamate decarboxylase 1 (GAD1) with phobias (P = 0.0005). A subsequent meta-analysis (N = 1985) incorporating previously published findings supported involvement of a single GAD1 risk haplotype in determining susceptibility to a broad range of internalizing disorders (P = 0.0009). We additionally found that SNPs and haplotypes in neuropeptide Y (NPY) modified the effect of childhood adversities on anxiety susceptibility (P = 0.003). In conclusion, we provide further support for involvement of mainly GAD1, but also NPY in determining predisposition to anxiety disorders. © 2012 Wiley Periodicals, Inc.

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