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

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MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits. / Hommers, Leif; Raab, Annette; Bohl, Alexandra; Weber, Heike; Scholz, Claus-Jürgen; Erhardt, Angelika; Binder, Elisabeth; Arolt, Volker; Gerlach, Alexander; Gloster, Andrew; Kalisch, Raffael; Kircher, Tilo; Lonsdorf, Tina; Ströhle, Andreas; Zwanzger, Peter; Mattheisen, Manuel; Cichon, Sven; Lesch, Klaus-Peter; Domschke, Katharina; Reif, Andreas; Lohse, Martin J; Deckert, Jürgen.

In: AM J MED GENET B, Vol. 168, No. 4, 06.2015, p. 296-306.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hommers, L, Raab, A, Bohl, A, Weber, H, Scholz, C-J, Erhardt, A, Binder, E, Arolt, V, Gerlach, A, Gloster, A, Kalisch, R, Kircher, T, Lonsdorf, T, Ströhle, A, Zwanzger, P, Mattheisen, M, Cichon, S, Lesch, K-P, Domschke, K, Reif, A, Lohse, MJ & Deckert, J 2015, 'MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits', AM J MED GENET B, vol. 168, no. 4, pp. 296-306. https://doi.org/10.1002/ajmg.b.32312

APA

Hommers, L., Raab, A., Bohl, A., Weber, H., Scholz, C-J., Erhardt, A., Binder, E., Arolt, V., Gerlach, A., Gloster, A., Kalisch, R., Kircher, T., Lonsdorf, T., Ströhle, A., Zwanzger, P., Mattheisen, M., Cichon, S., Lesch, K-P., Domschke, K., ... Deckert, J. (2015). MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits. AM J MED GENET B, 168(4), 296-306. https://doi.org/10.1002/ajmg.b.32312

Vancouver

Hommers L, Raab A, Bohl A, Weber H, Scholz C-J, Erhardt A et al. MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits. AM J MED GENET B. 2015 Jun;168(4):296-306. https://doi.org/10.1002/ajmg.b.32312

Bibtex

@article{4f4de79be8004ecb97dec4e2c5217b21,
title = "MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits",
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 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. {\textcopyright} 2015 Wiley Periodicals, Inc.",
author = "Leif Hommers and Annette Raab and Alexandra Bohl and Heike Weber and Claus-J{\"u}rgen Scholz and Angelika Erhardt and Elisabeth Binder and Volker Arolt and Alexander Gerlach and Andrew Gloster and Raffael Kalisch and Tilo Kircher and Tina Lonsdorf and Andreas Str{\"o}hle and Peter Zwanzger and Manuel Mattheisen and Sven Cichon and Klaus-Peter Lesch and Katharina Domschke and Andreas Reif and Lohse, {Martin J} and J{\"u}rgen Deckert",
note = "{\textcopyright} 2015 Wiley Periodicals, Inc.",
year = "2015",
month = jun,
doi = "10.1002/ajmg.b.32312",
language = "English",
volume = "168",
pages = "296--306",
journal = "AM J MED GENET B",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits

AU - Hommers, Leif

AU - Raab, Annette

AU - Bohl, Alexandra

AU - Weber, Heike

AU - Scholz, Claus-Jürgen

AU - Erhardt, Angelika

AU - Binder, Elisabeth

AU - Arolt, Volker

AU - Gerlach, Alexander

AU - Gloster, Andrew

AU - Kalisch, Raffael

AU - Kircher, Tilo

AU - Lonsdorf, Tina

AU - Ströhle, Andreas

AU - Zwanzger, Peter

AU - Mattheisen, Manuel

AU - Cichon, Sven

AU - Lesch, Klaus-Peter

AU - Domschke, Katharina

AU - Reif, Andreas

AU - Lohse, Martin J

AU - Deckert, Jürgen

N1 - © 2015 Wiley Periodicals, Inc.

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

U2 - 10.1002/ajmg.b.32312

DO - 10.1002/ajmg.b.32312

M3 - SCORING: Journal article

C2 - 25847876

VL - 168

SP - 296

EP - 306

JO - AM J MED GENET B

JF - AM J MED GENET B

SN - 1552-4841

IS - 4

ER -