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P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts

Authors

  • Pia Soronen,

    1. Public Health Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland
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  • Outi Mantere,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Tarja Melartin,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Kirsi Suominen,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Maria Vuorilehto,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Heikki Rytsälä,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Petri Arvilommi,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Irina Holma,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Mikael Holma,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Pekka Jylhä,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Hanna M. Valtonen,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland
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  • Jari Haukka,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
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  • Erkki Isometsä,

    1. Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
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  • Tiina Paunio

    Corresponding author
    1. Public Health Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Helsinki, Finland
    2. Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland
    • Public Health Genomics Unit and Institute for Molecular Medicine FIMM, National Institute for Health and Welfare, Biomedicum, P.O. Box 104, 00251 Helsinki, Finland.
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  • How to cite this article: Soronen P, Mantere O, Melartin T, Suominen K, Vuorilehto M, Rytsälä H, Arvilommi P, Holma I, Holma M, Jylhä P, Valtonen HM, Haukka J, Isometsä E, Paunio T. 2011. P2RX7 Gene Is Associated Consistently with Mood Disorders and Predicts Clinical Outcome in Three Clinical Cohorts. Am J Med Genet Part B 156:435–447.

Abstract

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM-IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6–83) months. Healthy control subjects (n = 1322) were obtained from the population-based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post-hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1–1.6, P = 0.0069 and OR 1.7, 95% CI 1.3–2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder. © 2011 Wiley-Liss, Inc.

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