Manuel Mattheisen

MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Leif Hommers, Unknown
  • Annette Raab, Unknown
  • Alexandra Bohl, Unknown
  • Heike Weber
  • ,
  • Claus-Jürgen Scholz
  • ,
  • Angelika Erhardt
  • ,
  • Elisabeth Binder
  • ,
  • Volker Arolt
  • ,
  • Alexander Gerlach
  • ,
  • Andrew Gloster, Unknown
  • Raffael Kalisch, Unknown
  • Tilo Kircher
  • ,
  • Tina Lonsdorf, Unknown
  • Andreas Ströhle
  • ,
  • Peter Zwanzger, Unknown
  • Manuel Mattheisen
  • Sven Cichon
  • ,
  • Klaus-Peter Lesch
  • ,
  • Katharina Domschke
  • ,
  • Andreas Reif
  • ,
  • Martin J Lohse, Unknown
  • Jürgen Deckert

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 npatients  = 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 (ncombined  = 831). Taken together, data indicate that MIR4717 regulates human RGS2 and contributes to the genetic risk towards anxiety-related traits. © 2015 Wiley Periodicals, Inc.

Original languageEnglish
JournalAmerican journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN1552-4841
DOIs
Publication statusPublished - 2 Apr 2015

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