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GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder
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dc.contributor.author | Deckert, Jürgen | |
dc.contributor.author | Weber, Heike | |
dc.contributor.author | Villmann, Carmen | |
dc.contributor.author | Lonsdorf, Tina B. | |
dc.contributor.author | Richter, Jan | |
dc.contributor.author | Andreatta, Marta | |
dc.contributor.author | Arias-Vasquez, Alejandro | |
dc.contributor.author | Hommers, Leif | |
dc.contributor.author | Kent, Lindsey | |
dc.contributor.author | Schartner, Christoph | |
dc.contributor.author | Cichon, Sven | |
dc.contributor.author | Wolf, Christian | |
dc.contributor.author | Schaefer, Natascha | |
dc.contributor.author | von Collenberg, Cora R. | |
dc.contributor.author | Wachter, Britta | |
dc.contributor.author | Blum, Robert | |
dc.contributor.author | Schümann, Dirk | |
dc.contributor.author | Scharfenort, Robert | |
dc.contributor.author | Schumacher, Johannes | |
dc.contributor.author | Forstner, Andreas J. | |
dc.contributor.author | Baumann, Christian | |
dc.contributor.author | Schiele, Miriam A. | |
dc.contributor.author | Notzon, Swantje | |
dc.contributor.author | Zwanzger, Peter | |
dc.contributor.author | Janzing, Joost G.E. | |
dc.contributor.author | Galesloot, Tessel | |
dc.contributor.author | Kiemeney, Lambertus A. | |
dc.contributor.author | Gajewska, Agnes | |
dc.contributor.author | Glotzbach-Schoon, Evelyn | |
dc.contributor.author | Mühlberger, Andreas | |
dc.contributor.author | Alpers, Georg | |
dc.contributor.author | Fydrich, Thomas | |
dc.contributor.author | Fehm, Lydia | |
dc.contributor.author | Gerlach, Alexander L. | |
dc.contributor.author | Kircher, Tilo | |
dc.contributor.author | Lang, Thomas | |
dc.contributor.author | Ströhle, Andreas | |
dc.contributor.author | Arolt, Volker | |
dc.contributor.author | Wittchen, Hans-Ulrich | |
dc.contributor.author | Kalisch, Raffael | |
dc.contributor.author | Büchel, Christian | |
dc.contributor.author | Hamm, Alfons | |
dc.contributor.author | Nöthen, Markus M. | |
dc.contributor.author | Romanos, Marcel | |
dc.contributor.author | Domschke, Katharina | |
dc.contributor.author | Pauli, Pauli | |
dc.contributor.author | Reif, Andreas | |
dc.date.accessioned | 2017-08-07T23:34:18Z | |
dc.date.available | 2017-08-07T23:34:18Z | |
dc.date.issued | 2017-10 | |
dc.identifier | 248518225 | |
dc.identifier | 172343af-f4af-4ca2-a550-bd540af0d41b | |
dc.identifier | 85011649906 | |
dc.identifier | 000411473400007 | |
dc.identifier.citation | Deckert , J , Weber , H , Villmann , C , Lonsdorf , T B , Richter , J , Andreatta , M , Arias-Vasquez , A , Hommers , L , Kent , L , Schartner , C , Cichon , S , Wolf , C , Schaefer , N , von Collenberg , C R , Wachter , B , Blum , R , Schümann , D , Scharfenort , R , Schumacher , J , Forstner , A J , Baumann , C , Schiele , M A , Notzon , S , Zwanzger , P , Janzing , J G E , Galesloot , T , Kiemeney , L A , Gajewska , A , Glotzbach-Schoon , E , Mühlberger , A , Alpers , G , Fydrich , T , Fehm , L , Gerlach , A L , Kircher , T , Lang , T , Ströhle , A , Arolt , V , Wittchen , H-U , Kalisch , R , Büchel , C , Hamm , A , Nöthen , M M , Romanos , M , Domschke , K , Pauli , P & Reif , A 2017 , ' GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder ' , Molecular Psychiatry , vol. 22 , no. 2 , pp. 1431-1439 . https://doi.org/10.1038/mp.2017.2 | en |
dc.identifier.issn | 1359-4184 | |
dc.identifier.other | ORCID: /0000-0002-5315-3399/work/60195366 | |
dc.identifier.uri | https://hdl.handle.net/10023/11399 | |
dc.description.abstract | The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG - related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10-8; rs191260602, p=3.9x10-8). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a case control sample with the categorical phenotype PD/AG (Ncombined =1,012) obtaining highly significant p-values also for GLRB single nucleotide variants rs17035816 (p=3.8x10-4) and rs7688285 (p=7.6x10-5). GLRB gene expression was found to be modulated by rs7688285 in brain tissue as well as cell culture. Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction withthe clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions. | |
dc.format.extent | 9 | |
dc.format.extent | 1790134 | |
dc.language.iso | eng | |
dc.relation.ispartof | Molecular Psychiatry | en |
dc.subject | Agoraphobia | en |
dc.subject | GWAS | en |
dc.subject | GLRB | en |
dc.subject | Startle | en |
dc.subject | Fear network | en |
dc.subject | Spastic mouse | en |
dc.subject | Panic disorder | en |
dc.subject | QH301 Biology | en |
dc.subject | QH426 Genetics | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | MCP | en |
dc.subject.lcc | QH301 | en |
dc.subject.lcc | QH426 | en |
dc.subject.lcc | RC0321 | en |
dc.title | GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation : a potential neurogenetic pathway to panic disorder | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.identifier.doi | 10.1038/mp.2017.2 | |
dc.description.status | Peer reviewed | en |
dc.date.embargoedUntil | 2017-08-07 |
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