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

Erhardt, A. and Czibere, L. and Roeske, D. and Lucae, S. and Unschuld, P. G. and Ripke, S. and Specht, M. and Kohli, M. A. and Kloiber, S. and Ising, M. and Heck, A. and Pfister, H. and Zimmermann, P. and Lieb, R. and Pütz, B. and Uhr, M. and Weber, P. and Deussing, J. M. and Gonik, M. and Bunck, M. and Kebler, M. S. and Frank, E. and Hohoff, C. and Domschke, K. and Krakowitzky, P. and Maier, W. and Bandelow, B. and Jacob, C. and Deckert, J. and Schreiber, S. and Strohmaier, J. and Nöthen, M. and Cichon, S. and Rietschel, M. and Bettecken, T. and Keck, M. E. and Landgraf, R. and Müller-Myhsok, B. and Holsboer, F. and Binder, E. B.. (2011) TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies. Molecular Psychiatry, 16 (6). pp. 647-663.

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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.
Faculties and Departments:07 Faculty of Psychology > Departement Psychologie
UniBasel Contributors:Heck, Angela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:04 Sep 2019 14:52
Deposited On:30 Nov 2017 08:05

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