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TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

Molecular Psychiatry volume 16, pages 647–663 (2011)Cite this article

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Abstract

The lifetime prevalence of panic disorder (PD) is up to 4% worldwide and there is substantial evidence that genetic factors contribute to the development of PD. Single-nucleotide polymorphisms (SNPs) in TMEM132D, identified in a whole-genome association study (GWAS), were found to be associated with PD in three independent samples, with a two-SNP haplotype associated in each of three samples in the same direction, and with a P-value of 1.2e−7 in the combined sample (909 cases and 915 controls). Independent SNPs in this gene were also associated with the severity of anxiety symptoms in patients affected by PD or panic attacks as well as in patients suffering from unipolar depression. Risk genotypes for PD were associated with higher TMEM132D mRNA expression levels in the frontal cortex. In parallel, using a mouse model of extremes in trait anxiety, we could further show that anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex, central to the processing of anxiety/fear-related stimuli, and that in this animal model a Tmem132d SNP is associated with anxiety-related behavior in an F2 panel. TMEM132D may thus be an important new candidate gene for PD as well as more generally for anxiety-related behavior.

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Acknowledgements

We thank G Ernst-Jansen, G Gajewsky, J Huber, E Kappelmann, S Sauer, S Damast, M Koedel, M Asmus and A Sangl for their excellent technical support. We also thank Rene Breuer from the Central Institute of Mental Health from Mannheim for excellent management of the blood and phenotypic database. Katharina Domschke and Jürgen Deckert were supported by the Deutsche Forschungsgemeinschaft (SFB-TRR-58 C2 and Z2). We thank the NGFN for a grant enabling the genotyping of PopGen subjects within the second round of funding. We thank further the NGFN MooDs and the Max Planck Excellence Foundation for grant support.

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Author notes

  1. R Lieb

    Present address: 10Current address: Institute of Psychology, University of Basel, Basel, Switzerland.,

  2. M E Keck

    Present address: 11Current address: Neuroscience Centre Zürich and Klinik Schlössli, Oetwil am See/Zurich, Switzerland.,

Authors and Affiliations

  1. Max Planck Institute of Psychiatry, München, Germany

    A Erhardt, L Czibere, D Roeske, S Lucae, P G Unschuld, S Ripke, M Specht, M A Kohli, S Kloiber, M Ising, A Heck, H Pfister, P Zimmermann, R Lieb, B Pütz, M Uhr, P Weber, J M Deussing, M Gonik, M Bunck, M S Keßler, E Frank, T Bettecken, M E Keck, R Landgraf, B Müller-Myhsok, F Holsboer & E B Binder

  2. Department of Psychiatry, University of Münster, Münster, Germany

    C Hohoff, K Domschke & P Krakowitzky

  3. Department of Psychiatry, University of Bonn, Bonn, Germany

    W Maier

  4. Department of Psychiatry, University of Göttingen, Göttingen, Germany

    B Bandelow

  5. Department of Psychiatry, University of Würzburg, Würzburg, Germany

    C Jacob & J Deckert

  6. Department of General Internal Medicine, Christian-Albrechts University, Kiel, Germany

    S Schreiber

  7. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany

    J Strohmaier & M Rietschel

  8. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    M Nöthen & S Cichon

  9. Institute of Human Genetics, University of Bonn, Bonn, Germany

    M Nöthen & S Cichon

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  1. A Erhardt
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Correspondence to A Erhardt.

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Erhardt, A., Czibere, L., Roeske, D. et al. TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies. Mol Psychiatry 16, 647–663 (2011). https://doi.org/10.1038/mp.2010.41

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