Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.

2.50
Hdl Handle:
http://hdl.handle.net/10146/618227
Title:
Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.
Authors:
Mühleisen, Thomas W; Reinbold, Céline S; Forstner, Andreas J; Abramova, Lilia I; Alda, Martin; Babadjanova, Gulja; Bauer, Michael; Brennan, Paul; Chuchalin, Alexander; Cruceanu, Cristiana; Czerski, Piotr M; Degenhardt, Franziska; Fischer, Sascha B; Fullerton, Janice M; Gordon, Scott D; Grigoroiu-Serbanescu, Maria; Grof, Paul; Hauser, Joanna; Hautzinger, Martin; Herms, Stefan; Hoffmann, Per; Kammerer-Ciernioch, Jutta; Khusnutdinova, Elza; Kogevinas, Manolis; Krasnov, Valery; Lacour, André; Laprise, Catherine; Leber, Markus; Lissowska, Jolanta; Lucae, Susanne; Maaser, Anna; Maier, Wolfgang; Martin, Nicholas G; Mattheisen, Manuel; Mayoral, Fermin; McKay, James D; Medland, Sarah E; Mitchell, Philip B; Moebus, Susanne; Montgomery, Grant W; Müller-Myhsok, Bertram; Oruc, Lilijana; Pantelejeva, Galina; Pfennig, Andrea; Pojskic, Lejla; Polonikov, Alexey; Reif, Andreas; Rivas, Fabio; Rouleau, Guy A; Schenk, Lorena M; Schofield, Peter R; Schwarz, Markus; Streit, Fabian; Strohmaier, Jana; Szeszenia-Dabrowska, Neonila; Tiganov, Alexander S; Treutlein, Jens; Turecki, Gustavo; Vedder, Helmut; Witt, Stephanie H; Schulze, Thomas G; Rietschel, Marcella; Nöthen, Markus M; Cichon, Sven
Abstract:
Bipolar 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.; We 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.; Two 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.; Pathway 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.; Pathway 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.
Affiliation:
Nofer Institute of Occupational Medicine
Citation:
J Affect Disord 2018, 228:20-25
Journal:
Journal of Affective Disorders
Issue Date:
2018
URI:
http://hdl.handle.net/10146/618227
DOI:
10.1016/j.jad.2017.11.068
PubMed ID:
29197740
Additional Links:
https://www.sciencedirect.com/science/article/pii/S0165032717315082?via%3Dihub
Type:
Article
Language:
en
ISSN:
1573-2517
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorMühleisen, Thomas Wen
dc.contributor.authorReinbold, Céline Sen
dc.contributor.authorForstner, Andreas Jen
dc.contributor.authorAbramova, Lilia Ien
dc.contributor.authorAlda, Martinen
dc.contributor.authorBabadjanova, Guljaen
dc.contributor.authorBauer, Michaelen
dc.contributor.authorBrennan, Paulen
dc.contributor.authorChuchalin, Alexanderen
dc.contributor.authorCruceanu, Cristianaen
dc.contributor.authorCzerski, Piotr Men
dc.contributor.authorDegenhardt, Franziskaen
dc.contributor.authorFischer, Sascha Ben
dc.contributor.authorFullerton, Janice Men
dc.contributor.authorGordon, Scott Den
dc.contributor.authorGrigoroiu-Serbanescu, Mariaen
dc.contributor.authorGrof, Paulen
dc.contributor.authorHauser, Joannaen
dc.contributor.authorHautzinger, Martinen
dc.contributor.authorHerms, Stefanen
dc.contributor.authorHoffmann, Peren
dc.contributor.authorKammerer-Ciernioch, Juttaen
dc.contributor.authorKhusnutdinova, Elzaen
dc.contributor.authorKogevinas, Manolisen
dc.contributor.authorKrasnov, Valeryen
dc.contributor.authorLacour, Andréen
dc.contributor.authorLaprise, Catherineen
dc.contributor.authorLeber, Markusen
dc.contributor.authorLissowska, Jolantaen
dc.contributor.authorLucae, Susanneen
dc.contributor.authorMaaser, Annaen
dc.contributor.authorMaier, Wolfgangen
dc.contributor.authorMartin, Nicholas Gen
dc.contributor.authorMattheisen, Manuelen
dc.contributor.authorMayoral, Ferminen
dc.contributor.authorMcKay, James Den
dc.contributor.authorMedland, Sarah Een
dc.contributor.authorMitchell, Philip Ben
dc.contributor.authorMoebus, Susanneen
dc.contributor.authorMontgomery, Grant Wen
dc.contributor.authorMüller-Myhsok, Bertramen
dc.contributor.authorOruc, Lilijanaen
dc.contributor.authorPantelejeva, Galinaen
dc.contributor.authorPfennig, Andreaen
dc.contributor.authorPojskic, Lejlaen
dc.contributor.authorPolonikov, Alexeyen
dc.contributor.authorReif, Andreasen
dc.contributor.authorRivas, Fabioen
dc.contributor.authorRouleau, Guy Aen
dc.contributor.authorSchenk, Lorena Men
dc.contributor.authorSchofield, Peter Ren
dc.contributor.authorSchwarz, Markusen
dc.contributor.authorStreit, Fabianen
dc.contributor.authorStrohmaier, Janaen
dc.contributor.authorSzeszenia-Dabrowska, Neonilaen
dc.contributor.authorTiganov, Alexander Sen
dc.contributor.authorTreutlein, Jensen
dc.contributor.authorTurecki, Gustavoen
dc.contributor.authorVedder, Helmuten
dc.contributor.authorWitt, Stephanie Hen
dc.contributor.authorSchulze, Thomas Gen
dc.contributor.authorRietschel, Marcellaen
dc.contributor.authorNöthen, Markus Men
dc.contributor.authorCichon, Svenen
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.en
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.en
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.en
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.en
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.en
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

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