Muehleisen, Thomas W., Reinbold, Celine S., Forstner, Andreas J., Abramova, Lilia I., Alda, Martin ORCID: 0000-0001-9544-3944, 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 ORCID: 0000-0002-1304-6687, Grof, Paul, Hauser, Joanna, Hautzinger, Martin, Herms, Stefan ORCID: 0000-0002-2786-8200, Hoffmann, Per, Kammerer-Ciernioch, Jutta, Khusnutdinova, Elza, Kogevinas, Manolis ORCID: 0000-0002-9605-0461, Krasnova, Valery, Lacour, Andre ORCID: 0000-0003-2692-2583, Laprise, Catherine ORCID: 0000-0001-5526-9945, Leber, Markus, Lissowska, Jolanta ORCID: 0000-0003-2695-5799, Lucae, Susanne, Maaser, Anna, Maier, Wolfgang, Martin, Nicholas G., Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Mayoral, Fermin, McKay, James D., Medland, Sarah E., Mitchell, Philip B., Moebus, Susanne, Montgomery, Grant W., Mueller-Myhsok, Bertram, Oruc, Lilijana, Pantelejeva, Galina, Pfennig, Andrea, Pojskic, Lejla, Polonikov, Alexey ORCID: 0000-0001-6280-247X, 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 ORCID: 0000-0003-4075-2736, Vedder, Helmut, Witt, Stephanie H., Schulze, Thomas G., Rietschel, Marcella, Noethen, Markus M. and Cichon, Sven ORCID: 0000-0002-9475-086X (2018). Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder. J. Affect. Disord., 228. S. 20 - 26. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1573-2517

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Abstract

Background: 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. Methods: 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. Results: 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 (P-FDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (P-FDR = 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. Limitations: 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. Conclusions: 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Muehleisen, Thomas W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinbold, Celine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forstner, Andreas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abramova, Lilia I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alda, MartinUNSPECIFIEDorcid.org/0000-0001-9544-3944UNSPECIFIED
Babadjanova, GuljaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brennan, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chuchalin, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cruceanu, CristianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czerski, Piotr M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, Sascha B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fullerton, Janice M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gordon, Scott D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grigoroiu-Serbanescu, MariaUNSPECIFIEDorcid.org/0000-0002-1304-6687UNSPECIFIED
Grof, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, JoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hautzinger, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, StefanUNSPECIFIEDorcid.org/0000-0002-2786-8200UNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kammerer-Ciernioch, JuttaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khusnutdinova, ElzaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kogevinas, ManolisUNSPECIFIEDorcid.org/0000-0002-9605-0461UNSPECIFIED
Krasnova, ValeryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacour, AndreUNSPECIFIEDorcid.org/0000-0003-2692-2583UNSPECIFIED
Laprise, CatherineUNSPECIFIEDorcid.org/0000-0001-5526-9945UNSPECIFIED
Leber, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lissowska, JolantaUNSPECIFIEDorcid.org/0000-0003-2695-5799UNSPECIFIED
Lucae, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maaser, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, Nicholas G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattheisen, ManuelUNSPECIFIEDorcid.org/0000-0002-8442-493XUNSPECIFIED
Mayoral, FerminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKay, James D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Medland, Sarah E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, Philip B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montgomery, Grant W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oruc, LilijanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantelejeva, GalinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfennig, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pojskic, LejlaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polonikov, AlexeyUNSPECIFIEDorcid.org/0000-0001-6280-247XUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rivas, FabioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouleau, Guy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schenk, Lorena M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schofield, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Streit, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strohmaier, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szeszenia-Dabrowska, NeonilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiganov, Alexander S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treutlein, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turecki, GustavoUNSPECIFIEDorcid.org/0000-0003-4075-2736UNSPECIFIED
Vedder, HelmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, Stephanie H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulze, Thomas G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, MarcellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichon, SvenUNSPECIFIEDorcid.org/0000-0002-9475-086XUNSPECIFIED
URN: urn:nbn:de:hbz:38-193475
DOI: 10.1016/j.jad.2017.11.068
Journal or Publication Title: J. Affect. Disord.
Volume: 228
Page Range: S. 20 - 26
Date: 2018
Publisher: ELSEVIER SCIENCE BV
Place of Publication: AMSTERDAM
ISSN: 1573-2517
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; GSA-SNP; NEUROCANMultiple languages
Clinical Neurology; PsychiatryMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19347

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