Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, p...

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Autores: Aranda, Selena, Muntané, Gerard, Vilella, Elisabet
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/360683
Acceso en línea:http://hdl.handle.net/10261/360683
Access Level:acceso abierto
Palabra clave:Biomarkers
Bipolar disorder
Schizophrenia
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spelling Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorderAranda, SelenaMuntané, GerardVilella, ElisabetBiomarkersBipolar disorderSchizophrenia© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.DDR1 has been linked to schizophrenia (SCZ) and bipolar disorder (BD) in association studies. DDR1 encodes 58 distinct transcripts, which can be translated into five isoforms (DDR1a-e) and are expressed in the brain. However, the transcripts expressed in each brain cell type, their functions and their involvement in SCZ and BD remain unknown. Here, to infer the processes in which DDR1 transcripts are involved, we used transcriptomic data from the human brain dorsolateral prefrontal cortex of healthy controls (N = 936) and performed weighted gene coexpression network analysis followed by enrichment analyses. Then, to explore the involvement of DDR1 transcripts in SCZ (N = 563) and BD (N = 222), we studied the association of coexpression modules with disease and performed differential expression and transcript significance analyses. Some DDR1 transcripts were distributed across five coexpression modules identified in healthy controls (MHC). MHC1 and MHC2 were enriched in the cell cycle and proliferation of astrocytes and OPCs; MHC3 and MHC4 were enriched in oligodendrocyte differentiation and myelination; and MHC5 was enriched in neurons and synaptic transmission. Most of the DDR1 transcripts associated with SCZ and BD pertained to MHC1 and MHC2. Altogether, our results suggest that DDR1 expression might be altered in SCZ and BD via the proliferation of astrocytes and OPCs, suggesting that these processes are relevant in psychiatric disorders.The study was supported by grants from the Brain and Behavior Research Foundation (2017 NARSAD Independent grant, #25811 to EV), Instituto de Salud Carlos III (Research Project PI18/00954 to EV), and Agència de Gestió d’Ajuts Universitaris i de Recerca (2021SGR01065 to EV). Selena Aranda was the recipient of a predoctoral fellowship granted by the Instituto de Salud Carlos III (PFIS FI19/00268).Peer reviewedMultidisciplinary Digital Publishing InstituteBrain and Behavior Research FoundationInstituto de Salud Carlos IIIAgència de Gestió d'Ajuts Universitaris i de RecercaMuntané, Gerard [0000-0003-1541-8365]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/360683reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00954The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1038/s41398-024-02823-0https://doi.org/10.1038/s41398-024-02823-0Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3606832026-05-22T06:33:51Z
dc.title.none.fl_str_mv Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
title Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
spellingShingle Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
Aranda, Selena
Biomarkers
Bipolar disorder
Schizophrenia
title_short Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
title_full Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
title_fullStr Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
title_full_unstemmed Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
title_sort Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder
dc.creator.none.fl_str_mv Aranda, Selena
Muntané, Gerard
Vilella, Elisabet
author Aranda, Selena
author_facet Aranda, Selena
Muntané, Gerard
Vilella, Elisabet
author_role author
author2 Muntané, Gerard
Vilella, Elisabet
author2_role author
author
dc.contributor.none.fl_str_mv Brain and Behavior Research Foundation
Instituto de Salud Carlos III
Agència de Gestió d'Ajuts Universitaris i de Recerca
Muntané, Gerard [0000-0003-1541-8365]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Biomarkers
Bipolar disorder
Schizophrenia
topic Biomarkers
Bipolar disorder
Schizophrenia
description © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/360683
url http://hdl.handle.net/10261/360683
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F00954
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1038/s41398-024-02823-0
https://doi.org/10.1038/s41398-024-02823-0
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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