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Data from rodent models and genetic analysis of anxiety\u2010related traits and disorders in humans suggest down\u2010regulation of RGS2 expression to be a risk factor for anxiety. Here we investigated, whether genetic variation in microRNAs mediating posttranscriptional down\u2010regulation of RGS2 may be a risk factor for anxiety as well. 75 microRNAs predicted to regulate <jats:italic>RGS2<\/jats:italic> were identified by four bioinformatic algorithms and validated experimentally by luciferase reporter gene assays. Specificity was confirmed for six microRNAs (hsa\u2010miR\u20101271\u20105p, hsa\u2010miR\u201022\u20103p, hsa\u2010miR\u20103591\u20103p, hsa\u2010miR\u2010377\u20103p, hsa\u2010miR\u20104717\u20105p, hsa\u2010miR\u201096\u20105p) by disrupting their seed sequence at the 3\u2032 untranslated region of <jats:italic>RGS2<\/jats:italic>. Hsa\u2010miR\u20104717\u20105p showed the most robust effect on <jats:italic>RGS2<\/jats:italic> and regulated two other candidate genes of anxiety disorders (<jats:italic>CNR1<\/jats:italic> and <jats:italic>IKBKE<\/jats:italic>) as well. Two SNPs (rs150925, rs161427) within and 1,000 bp upstream of the hostgene of hsa\u2010miR\u20104717\u20105p (<jats:italic>MIR4717<\/jats:italic>) show a minor allele frequency greater than 0.05. Both were in high linkage disequilibrium (r<jats:sup>2<\/jats:sup>\u2009=\u20091, D\u2032\u2009=\u20091) 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<jats:sub>patients<\/jats:sub>\u2009=\u2009497). 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<jats:sub>combined<\/jats:sub>\u2009=\u2009831). Taken together, data indicate that <jats:italic>MIR4717<\/jats:italic> regulates human RGS2 and contributes to the genetic risk towards anxiety\u2010related traits. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.b.32312","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T22:25:46Z","timestamp":1428013546000},"page":"296-306","source":"Crossref","is-referenced-by-count":22,"title":["MicroRNA hsa\u2010miR\u20104717\u20105p regulates RGS2 and may be a risk factor for anxiety\u2010related traits"],"prefix":"10.1002","volume":"168","author":[{"given":"Leif","family":"Hommers","sequence":"first","affiliation":[{"name":"Center of Mental Health Department of Psychiatry Psychosomatics and Psychotherapy University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"},{"name":"Interdisciplinary Center for Clinical Research University Hospital of W\u00fcrzburg W\u00fcrzburg Germany"},{"name":"Comprehensive Heart Failure Center (CHFC) 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