Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways

Margarita Muiños-Gimeno, Yolanda Espinosa-Parrilla, Monica Guidi, Birgit Kagerbauer, Tessa Sipilä, Eduard Maron, Kristi Pettai, Laura Kananen, Ricard Navinés, Rocío Martín-Santos, Mònica Gratacòs, Andres Metspalu, Iiris Hovatta, Xavier P. Estivill

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Background: The involvement of microRNAs (miRNAs) in neuronal differentiation and synaptic plasticity suggests a role for miRNAs in psychiatric disorders; association analyses and functional approaches were used to evaluate the implication of miRNAs in the susceptibility for panic disorder. Methods: Case-control studies for 712 single-nucleotide polymorphisms (SNPs) tagging 325 human miRNA regions were performed in 203 Spanish patients with panic disorder and 341 control subjects. A sample of 321 anxiety patients and 642 control subjects from Finland and 102 panic disorder patients and 829 control subjects from Estonia was used as a replica. Reporter-gene assays and miRNA overexpression experiments in neuroblastoma cells were used to functionally evaluate the spectrum of genes regulated by the associated miRNAs. Results: Two SNPs associated with panic disorder: rs6502892 tagging miR-22 (p < .0002), and rs11763020 tagging miR-339 (p < .00008). Other SNPs tagging miR-138-2, miR-488, miR-491, and miR-148a regions associated with different panic disorder phenotypes. Replication in the north-European sample supported several of these associations, although they did not pass correction for multiple testing. Functional studies revealed that miR-138-2, miR-148a, and miR-488 repress (30%-60%) several candidate genes for panic disorder - GABRA6, CCKBR and POMC, respectively - and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA, and RGS2. Transcriptome analysis of neuroblastoma cells transfected with miR-22 and miR-488 showed altered expression of a subset of predicted target genes for these miRNAs and of genes that might be affecting physiological pathways related to anxiety. Conclusions: This work represents the first report of a possible implication of miRNAs in the etiology of panic disorder.

Original languageEnglish
Pages (from-to)526-533
Number of pages8
JournalBiological Psychiatry
Volume69
Issue number6
DOIs
Publication statusPublished - 15 Mar 2011
Externally publishedYes

Fingerprint

Panic Disorder
MicroRNAs
Anxiety
Genes
Single Nucleotide Polymorphism
Neuronal Plasticity
Neuroblastoma
Estonia
Pro-Opiomelanocortin
human MIRN22 microRNA
Brain-Derived Neurotrophic Factor
Gene Expression Profiling
Finland
Reporter Genes
Psychiatry
Case-Control Studies
Phenotype

Keywords

  • Anxiety
  • association study
  • candidate gene
  • microRNAs
  • panic disorder
  • postranscriptional regulation

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways. / Muiños-Gimeno, Margarita; Espinosa-Parrilla, Yolanda; Guidi, Monica; Kagerbauer, Birgit; Sipilä, Tessa; Maron, Eduard; Pettai, Kristi; Kananen, Laura; Navinés, Ricard; Martín-Santos, Rocío; Gratacòs, Mònica; Metspalu, Andres; Hovatta, Iiris; Estivill, Xavier P.

In: Biological Psychiatry, Vol. 69, No. 6, 15.03.2011, p. 526-533.

Research output: Contribution to journalArticle

Muiños-Gimeno, M, Espinosa-Parrilla, Y, Guidi, M, Kagerbauer, B, Sipilä, T, Maron, E, Pettai, K, Kananen, L, Navinés, R, Martín-Santos, R, Gratacòs, M, Metspalu, A, Hovatta, I & Estivill, XP 2011, 'Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways', Biological Psychiatry, vol. 69, no. 6, pp. 526-533. https://doi.org/10.1016/j.biopsych.2010.10.010
Muiños-Gimeno, Margarita ; Espinosa-Parrilla, Yolanda ; Guidi, Monica ; Kagerbauer, Birgit ; Sipilä, Tessa ; Maron, Eduard ; Pettai, Kristi ; Kananen, Laura ; Navinés, Ricard ; Martín-Santos, Rocío ; Gratacòs, Mònica ; Metspalu, Andres ; Hovatta, Iiris ; Estivill, Xavier P. / Human microRNAs miR-22, miR-138-2, miR-148a, and miR-488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways. In: Biological Psychiatry. 2011 ; Vol. 69, No. 6. pp. 526-533.
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AU - Muiños-Gimeno, Margarita

AU - Espinosa-Parrilla, Yolanda

AU - Guidi, Monica

AU - Kagerbauer, Birgit

AU - Sipilä, Tessa

AU - Maron, Eduard

AU - Pettai, Kristi

AU - Kananen, Laura

AU - Navinés, Ricard

AU - Martín-Santos, Rocío

AU - Gratacòs, Mònica

AU - Metspalu, Andres

AU - Hovatta, Iiris

AU - Estivill, Xavier P.

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KW - candidate gene

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KW - postranscriptional regulation

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