RT Journal Article
T1 Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.
A1 Muhleisen, Thomas W
A1 Reinbold, Celine S
A1 Forstner, Andreas J
A1 Abramova, Lilia I
A1 Alda, Martin
A1 Babadjanova, Gulja
A1 Bauer, Michael
A1 Brennan, Paul
A1 Chuchalin, Alexander
A1 Cruceanu, Cristiana
A1 Czerski, Piotr M
A1 Degenhardt, Franziska
A1 Fischer, Sascha B
A1 Fullerton, Janice M
A1 Gordon, Scott D
A1 Grigoroiu-Serbanescu, Maria
A1 Grof, Paul
A1 Hauser, Joanna
A1 Hautzinger, Martin
A1 Herms, Stefan
A1 Hoffmann, Per
A1 Kammerer-Ciernioch, Jutta
A1 Khusnutdinova, Elza
A1 Kogevinas, Manolis
A1 Krasnov, Valery
A1 Lacour, Andre
A1 Laprise, Catherine
A1 Leber, Markus
A1 Lissowska, Jolanta
A1 Lucae, Susanne
A1 Maaser, Anna
A1 Maier, Wolfgang
A1 Martin, Nicholas G
A1 Mattheisen, Manuel
A1 Mayoral, Fermin
A1 McKay, James D
A1 Medland, Sarah E
A1 Mitchell, Philip B
A1 Moebus, Susanne
A1 Montgomery, Grant W
A1 Muller-Myhsok, Bertram
A1 Oruc, Lilijana
A1 Pantelejeva, Galina
A1 Pfennig, Andrea
A1 Pojskic, Lejla
A1 Polonikov, Alexey
A1 Reif, Andreas
A1 Rivas, Fabio
A1 Rouleau, Guy A
A1 Schenk, Lorena M
A1 Schofield, Peter R
A1 Schwarz, Markus
A1 Streit, Fabian
A1 Strohmaier, Jana
A1 Szeszenia-Dabrowska, Neonila
A1 Tiganov, Alexander S
A1 Treutlein, Jens
A1 Turecki, Gustavo
A1 Vedder, Helmut
A1 Witt, Stephanie H
A1 Schulze, Thomas G
A1 Rietschel, Marcella
A1 Nothen, Markus M
A1 Cichon, Sven
K1 Bipolar disorder
K1 GRB2 events in ERBB2 signaling
K1 NCAM signaling for neurite out-growth
K1 Neurodevelopmental disorder
K1 Pathway analysis
AB 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.
PB Elsevier
YR 2018
FD 2018-01-04
LK http://hdl.handle.net/10668/11867
UL http://hdl.handle.net/10668/11867
LA en
NO Mühleisen TW, Reinbold CS, Forstner AJ, Abramova LI, Alda M, Babadjanova G, et al. Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. J Affect Disord. 2018 Mar 1;228:20-25
DS RISalud
RD Apr 7, 2025