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000841704 0247_ $$2doi$$a10.1016/j.jad.2017.11.068
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000841704 1001_ $$0P:(DE-Juel1)156419$$aMühleisen, Thomas$$b0
000841704 245__ $$aGene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder
000841704 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2018
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000841704 520__ $$aBipolar 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.
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000841704 7001_ $$aReinbold, Céline S$$b1
000841704 7001_ $$aForstner, Andreas J$$b2
000841704 7001_ $$aAbramova, Lilia I$$b3
000841704 7001_ $$aAlda, Martin$$b4
000841704 7001_ $$aBabadjanova, Gulja$$b5
000841704 7001_ $$aBauer, Michael$$b6
000841704 7001_ $$aBrennan, Paul$$b7
000841704 7001_ $$aChuchalin, Alexander$$b8
000841704 7001_ $$aCruceanu, Cristiana$$b9
000841704 7001_ $$aCzerski, Piotr M$$b10
000841704 7001_ $$aDegenhardt, Franziska$$b11
000841704 7001_ $$aFischer, Sascha B$$b12
000841704 7001_ $$aFullerton, Janice M$$b13
000841704 7001_ $$aGordon, Scott D$$b14
000841704 7001_ $$aGrigoroiu-Serbanescu, Maria$$b15
000841704 7001_ $$aGrof, Paul$$b16
000841704 7001_ $$aHauser, Joanna$$b17
000841704 7001_ $$aHautzinger, Martin$$b18
000841704 7001_ $$aHerms, Stefan$$b19
000841704 7001_ $$aHoffmann, Per$$b20
000841704 7001_ $$aKammerer-Ciernioch, Jutta$$b21
000841704 7001_ $$aKhusnutdinova, Elza$$b22
000841704 7001_ $$aKogevinas, Manolis$$b23
000841704 7001_ $$aKrasnov, Valery$$b24
000841704 7001_ $$aLacour, André$$b25
000841704 7001_ $$aLaprise, Catherine$$b26
000841704 7001_ $$aLeber, Markus$$b27
000841704 7001_ $$aLissowska, Jolanta$$b28
000841704 7001_ $$aLucae, Susanne$$b29
000841704 7001_ $$aMaaser, Anna$$b30
000841704 7001_ $$aMaier, Wolfgang$$b31
000841704 7001_ $$aMartin, Nicholas G$$b32
000841704 7001_ $$aMattheisen, Manuel$$b33
000841704 7001_ $$aMayoral, Fermin$$b34
000841704 7001_ $$aMcKay, James D$$b35
000841704 7001_ $$aMedland, Sarah E$$b36
000841704 7001_ $$aMitchell, Philip B$$b37
000841704 7001_ $$aMoebus, Susanne$$b38
000841704 7001_ $$aMontgomery, Grant W$$b39
000841704 7001_ $$aMüller-Myhsok, Bertram$$b40
000841704 7001_ $$aOruc, Lilijana$$b41
000841704 7001_ $$aPantelejeva, Galina$$b42
000841704 7001_ $$aPfennig, Andrea$$b43
000841704 7001_ $$aPojskic, Lejla$$b44
000841704 7001_ $$aPolonikov, Alexey$$b45
000841704 7001_ $$aReif, Andreas$$b46
000841704 7001_ $$aRivas, Fabio$$b47
000841704 7001_ $$aRouleau, Guy A$$b48
000841704 7001_ $$aSchenk, Lorena M$$b49
000841704 7001_ $$aSchofield, Peter R$$b50
000841704 7001_ $$aSchwarz, Markus$$b51
000841704 7001_ $$aStreit, Fabian$$b52
000841704 7001_ $$aStrohmaier, Jana$$b53
000841704 7001_ $$aSzeszenia-Dabrowska, Neonila$$b54
000841704 7001_ $$aTiganov, Alexander S$$b55
000841704 7001_ $$aTreutlein, Jens$$b56
000841704 7001_ $$aTurecki, Gustavo$$b57
000841704 7001_ $$aVedder, Helmut$$b58
000841704 7001_ $$aWitt, Stephanie H$$b59
000841704 7001_ $$aSchulze, Thomas G$$b60
000841704 7001_ $$aRietschel, Marcella$$b61
000841704 7001_ $$aNöthen, Markus M$$b62
000841704 7001_ $$0P:(DE-Juel1)140234$$aCichon, Sven$$b63$$eCorresponding author
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