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MicroRNA hsa-miR-4717-5p Regulates RGS2 and May Be a Risk Factor for Anxiety-Related Traits

Hommers, Leif and Raab, Annette and Bohl, Alexandra and Weber, Heike and Scholz, Claus-Jürgen and Erhardt, Angelika and Binder, Elisabeth and Arolt, Volker and Gerlach, Alexander and Gloster, Andrew and Kalisch, Raffael and Kircher, Tilo and Lonsdorf, Tina and Ströhle, Andreas and Zwanzger, Peter and Mattheisen, Manuel and Cichon, Sven and Lesch, Klaus-Peter and Domschke, Katharina and Reif, Andreas and Lohse, Martin J. and Deckert, Jürgen. (2015) MicroRNA hsa-miR-4717-5p Regulates RGS2 and May Be a Risk Factor for Anxiety-Related Traits. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics , 168B (4). pp. 296-306.

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Official URL: https://edoc.unibas.ch/61553/

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Abstract

Regulator of G-protein Signaling 2 (RGS2) is a key regulator of G-protein-coupled signaling pathways involved in fear and anxiety. Data from rodent models and genetic analysis of anxiety-related traits and disorders in humans suggest down-regulation of RGS2 expression to be a risk factor for anxiety. Here we investigated, whether genetic variation in microRNAs mediating posttranscriptional down-regulation of RGS2 may be a risk factor for anxiety as well. 75 microRNAs predicted to regulate RGS2 were identified by four bioinformatic algorithms and validated experimentally by luciferase reporter gene assays. Specificity was confirmed for six microRNAs (hsa-miR-1271-5p, hsa-miR-22-3p, hsa-miR-3591-3p, hsa-miR-377-3p, hsa-miR-4717-5p, hsa-miR-96-5p) by disrupting their seed sequence at the 3' untranslated region of RGS2. Hsa-miR-4717-5p showed the most robust effect on RGS2 and regulated two other candidate genes of anxiety disorders (CNR1 and IKBKE) as well. Two SNPs (rs150925, rs161427) within and 1,000 bp upstream of the hostgene of hsa-miR-4717-5p (MIR4717) show a minor allele frequency greater than 0.05. Both were in high linkage disequilibrium (r(2) = 1, D' = 1) and both major (G) alleles showed a trend for association with panic disorder with comorbid agoraphobia in one of two patient/control samples (combined n(patients) = 497). Dimensional anxiety traits, as described by Anxiety Sensitivity Index (ASI) and Agoraphobic Cognitions Questionnaire (ACQ) were significantly higher among carriers of both major (G) alleles in a combined patient/control sample (n(combined) = 831). Taken together, data indicate that MIR4717 regulates human RGS2 and contributes to the genetic risk towards anxiety-related traits.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-Blackwell - STM
ISSN: 1552-4841
e-ISSN:1552-485X
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:19 Sep 2018 10:53
Deposited On:19 Sep 2018 10:53

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