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dc.contributor.authorMühleisen, Thomas W
dc.contributor.authorReinbold, Céline S
dc.contributor.authorForstner, Andreas J
dc.contributor.authorAbramova, Lilia I
dc.contributor.authorAlda, Martin
dc.contributor.authorBabadjanova, Gulja
dc.contributor.authorBauer, Michael
dc.contributor.authorBrennan, Paul
dc.contributor.authorChuchalin, Alexander
dc.contributor.authorCruceanu, Cristiana
dc.contributor.authorCzerski, Piotr M
dc.contributor.authorDegenhardt, Franziska
dc.contributor.authorFischer, Sascha B
dc.contributor.authorFullerton, Janice M
dc.contributor.authorGordon, Scott D
dc.contributor.authorGrigoroiu-Serbanescu, Maria
dc.contributor.authorGrof, Paul
dc.contributor.authorHauser, Joanna
dc.contributor.authorHautzinger, Martin
dc.contributor.authorHerms, Stefan
dc.contributor.authorHoffmann, Per
dc.contributor.authorKammerer-Ciernioch, Jutta
dc.contributor.authorKhusnutdinova, Elza
dc.contributor.authorKogevinas, Manolis
dc.contributor.authorKrasnov, Valery
dc.contributor.authorLacour, André
dc.contributor.authorLaprise, Catherine
dc.contributor.authorLeber, Markus
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorLucae, Susanne
dc.contributor.authorMaaser, Anna
dc.contributor.authorMaier, Wolfgang
dc.contributor.authorMartin, Nicholas G
dc.contributor.authorMattheisen, Manuel
dc.contributor.authorMayoral, Fermin
dc.contributor.authorMcKay, James D
dc.contributor.authorMedland, Sarah E
dc.contributor.authorMitchell, Philip B
dc.contributor.authorMoebus, Susanne
dc.contributor.authorMontgomery, Grant W
dc.contributor.authorMüller-Myhsok, Bertram
dc.contributor.authorOruc, Lilijana
dc.contributor.authorPantelejeva, Galina
dc.contributor.authorPfennig, Andrea
dc.contributor.authorPojskic, Lejla
dc.contributor.authorPolonikov, Alexey
dc.contributor.authorReif, Andreas
dc.contributor.authorRivas, Fabio
dc.contributor.authorRouleau, Guy A
dc.contributor.authorSchenk, Lorena M
dc.contributor.authorSchofield, Peter R
dc.contributor.authorSchwarz, Markus
dc.contributor.authorStreit, Fabian
dc.contributor.authorStrohmaier, Jana
dc.contributor.authorSzeszenia-Dabrowska, Neonila
dc.contributor.authorTiganov, Alexander S
dc.contributor.authorTreutlein, Jens
dc.contributor.authorTurecki, Gustavo
dc.contributor.authorVedder, Helmut
dc.contributor.authorWitt, Stephanie H
dc.contributor.authorSchulze, Thomas G
dc.contributor.authorRietschel, Marcella
dc.contributor.authorNöthen, Markus M
dc.contributor.authorCichon, Sven
dc.date.accessioned2018-12-04T09:13:18Z
dc.date.available2018-12-04T09:13:18Z
dc.date.issued2018
dc.identifier.citationJ Affect Disord 2018, 228:20-25en
dc.identifier.issn1573-2517
dc.identifier.pmid29197740
dc.identifier.doi10.1016/j.jad.2017.11.068
dc.identifier.urihttp://hdl.handle.net/10146/618227
dc.description.abstractBipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci.
dc.description.abstractWe conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan.
dc.description.abstractTwo pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system.
dc.description.abstractPathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients.
dc.description.abstractPathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.
dc.language.isoenen
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0165032717315082?via%3Dihuben
dc.rightsArchived with thanks to Journal of affective disordersen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectbipolar disorderen
dc.subjectPathway analysisen
dc.subjectGRB2 events in ERBB2 signalingen
dc.subjectNCAM signaling for neurite out-growthen
dc.subjectNeurodevelopmental disorderen
dc.subject.meshAlgorithms
dc.subject.meshBipolar Disorder
dc.subject.meshBrain
dc.subject.meshFemale
dc.subject.meshGRB2 Adaptor Protein
dc.subject.meshGene Expression
dc.subject.meshGenes, erbB-2
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenome-Wide Association Study
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshPhenotype
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshRNA
dc.subject.meshReceptor, ErbB-2
dc.subject.meshSignal Transduction
dc.titleGene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicineen
dc.identifier.journalJournal of Affective Disordersen
html.description.abstractBipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci.
html.description.abstractWe conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan.
html.description.abstractTwo pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system.
html.description.abstractPathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients.
html.description.abstractPathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.


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Archived with thanks to Journal of affective disorders
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