Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder
| Autor: | Michael Bauer, Susanne Moebus, Gulja Babadjanova, Guy A. Rouleau, Sascha B. Fischer, Markus Schwarz, Gustavo Turecki, Wolfgang Maier, Helmut Vedder, Marcella Rietschel, Fabio Rivas, Jana Strohmaier, André Lacour, Catherine Laprise, Lilia I. Abramova, Alexey Polonikov, Nicholas G. Martin, Jolanta Lissowska, Lilijana Oruc, Andreas Reif, Joanna Hauser, Scott D. Gordon, Lorena M. Schenk, James McKay, Alexander S. Tiganov, Markus M. Nöthen, Grant W. Montgomery, Bertram Müller-Myhsok, Susanne Lucae, Neonila Szeszenia-Dabrowska, Martin Alda, Galina Pantelejeva, Céline S. Reinbold, Cristiana Cruceanu, Lejla Pojskic, Manolis Kogevinas, Thomas G. Schulze, Paul Grof, Alexander Chuchalin, Stephanie H. Witt, Jens Treutlein, Manuel Mattheisen, Sven Cichon, Janice M. Fullerton, Andreas J. Forstner, Fabian Streit, Elza Khusnutdinova, Martin Hautzinger, Paul Brennan, Sarah E. Medland, Fermín Mayoral, Anna Maaser, Piotr M. Czerski, Franziska Degenhardt, Per Hoffmann, Markus Leber, Valery Krasnov, Thomas W. Mühleisen, Peter R. Schofield, Stefan Herms, Philip B. Mitchell, Andrea Pfennig, Jutta Kammerer-Ciernioch, Maria Grigoroiu-Serbanescu |
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| Přispěvatelé: | Nofer Institute of Occupational Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Bipolar Disorder Pathway analysis Receptor ErbB-2 Medizin Gene Expression Genome-wide association study genetics [GRB2 Adaptor Protein] 0302 clinical medicine Neurodevelopmental disorder Gene expression GRB2 protein human physiology [Genes erbB-2] growth & development [Brain] Brain Psychiatry and Mental health Clinical Psychology Phenotype metabolism [RNA] Female Psychology Algorithms Signal Transduction metabolism [Receptor ErbB-2] physiopathology [Bipolar Disorder] Bipolar disorder Computational biology Polymorphism Single Nucleotide 03 medical and health sciences medicine Humans Genetic Predisposition to Disease ddc:610 Gene Genetic association GRB2 Adaptor Protein metabolism [Bipolar Disorder] metabolism [GRB2 Adaptor Protein] NCAM signaling for neurite out-growth RNA Genes erbB-2 medicine.disease GRB2 events in ERBB2 signaling 030104 developmental biology metabolism [Brain] Multiple comparisons problem Neuroscience 030217 neurology & neurosurgery genetics [Bipolar Disorder] Genome-Wide Association Study |
| Zdroj: | Mühleisen, T W, Reinbold, C S, Forstner, A J, Abramova, L I, Alda, M, Babadjanova, G, Bauer, M, Brennan, P, Chuchalin, A, Cruceanu, C, Czerski, P M, Degenhardt, F, Fischer, S B, Fullerton, J M, Gordon, S D, Grigoroiu-Serbanescu, M, Grof, P, Hauser, J, Hautzinger, M, Herms, S, Hoffmann, P, Kammerer-Ciernioch, J, Khusnutdinova, E, Kogevinas, M, Krasnov, V, Lacour, A, Laprise, C, Leber, M, Lissowska, J, Lucae, S, Maaser, A, Maier, W, Martin, N G, Mattheisen, M, Mayoral, F, McKay, J D, Medland, S E, Mitchell, P B, Moebus, S, Montgomery, G W, Müller-Myhsok, B, Oruc, L, Pantelejeva, G, Pfennig, A, Pojskic, L, Polonikov, A, Reif, A, Rivas, F, Rouleau, G A, Schenk, L M, Schofield, P R, Schwarz, M, Streit, F, Strohmaier, J, Szeszenia-Dabrowska, N, Tiganov, A S, Treutlein, J, Turecki, G, Vedder, H, Witt, S H, Schulze, T G, Rietschel, M, Nöthen, M M & Cichon, S 2018, ' Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder ', Journal of Affective Disorders, vol. 228, pp. 20-25 . https://doi.org/10.1016/j.jad.2017.11.068 JOURNAL OF AFFECTIVE DISORDERS Journal of affective disorders 228, 20-25 (2018). doi:10.1016/j.jad.2017.11.068 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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