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Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder

Forstner, A. J. and Hofmann, A. and Maaser, A. and Sumer, S. and Khudayberdiev, S. and Muhleisen, T. W. and Leber, M. and Schulze, T. G. and Strohmaier, J. and Degenhardt, F. and Treutlein, J. and Mattheisen, M. and Schumacher, J. and Breuer, R. and Meier, S. and Herms, S. and Hoffmann, P. and Lacour, A. and Witt, S. H. and Reif, A. and Muller-Myhsok, B. and Lucae, S. and Maier, W. and Schwarz, M. and Vedder, H. and Kammerer-Ciernioch, J. and Pfennig, A. and Bauer, M. and Hautzinger, M. and Moebus, S. and Priebe, L. and Sivalingam, S. and Verhaert, A. and Schulz, H. and Czerski, P. M. and Hauser, J. and Lissowska, J. and Szeszenia-Dabrowska, N. and Brennan, P. and McKay, J. D. and Wright, A. and Mitchell, P. B. and Fullerton, J. M. and Schofield, P. R. and Montgomery, G. W. and Medland, S. E. and Gordon, S. D. and Martin, N. G. and Krasnov, V. and Chuchalin, A. and Babadjanova, G. and Pantelejeva, G. and Abramova, L. I. and Tiganov, A. S. and Polonikov, A. and Khusnutdinova, E. and Alda, M. and Cruceanu, C. and Rouleau, G. A. and Turecki, G. and Laprise, C. and Rivas, F. and Mayoral, F. and Kogevinas, M. and Grigoroiu-Serbanescu, M. and Propping, P. and Becker, T. and Rietschel, M. and Cichon, S. and Schratt, G. and Nothen, M. M.. (2015) Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder. Translational Psychiatry , 5. e678.

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Official URL: https://edoc.unibas.ch/61545/

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Abstract

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2158-3188
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Oct 2018 18:56
Deposited On:16 Oct 2018 17:08

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