Forstner, A. J., Hofmann, A., Maaser, A., Sumer, S., Khudayberdiev, S., Muehleisen, T. W., Leber, M., Schulze, T. G., Strohmaier, J., Degenhardt, F., Treutlein, J., Mattheisen, M., Schumacher, J., Breuer, R., Meier, S., Herms, S., Hoffmann, P., Lacour, A., Witt, S. H., Reif, A., Mueller-Myhsok, B., Lucae, S., Maier, W., Schwarz, M., Vedder, H., Kammerer-Ciernioch, J., Pfennig, A., Bauer, M., Hautzinger, M., Moebus, S., Priebe, L., Sivalingam, S., Verhaert, A., Schulz, H., Czerski, P. M., Hauser, J., Lissowska, J., Szeszenia-Dabrowska, N., Brennan, P., McKay, J. D., Wright, A., Mitchell, P. B., Fullerton, J. M., Schofield, P. R., Montgomery, G. W., Medland, S. E., Gordon, S. D., Martin, N. G., Krasnov, V., Chuchalin, A., Babadjanova, G., Pantelejeva, G., Abramova, L. I., Tiganov, A. S., Polonikov, A., Khusnutdinova, E., Alda, M., Cruceanu, C., Rouleau, G. A., Turecki, G., Laprise, C., Rivas, F., Mayoral, F., Kogevinas, M., Grigoroiu-Serbanescu, M., Propping, P., Becker, T., Rietschel, M., Cichon, S., Schratt, G. and Noethen, M. M. (2015). Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder. Transl. Psychiatr., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2158-3188

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Forstner, A. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maaser, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sumer, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khudayberdiev, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muehleisen, T. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leber, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulze, T. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strohmaier, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treutlein, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattheisen, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Breuer, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacour, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witt, S. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Myhsok, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lucae, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maier, W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwarz, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vedder, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kammerer-Ciernioch, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfennig, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hautzinger, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Priebe, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sivalingam, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verhaert, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulz, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czerski, P. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hauser, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lissowska, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Szeszenia-Dabrowska, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brennan, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKay, J. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mitchell, P. B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fullerton, J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schofield, P. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montgomery, G. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Medland, S. E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gordon, S. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, N. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krasnov, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chuchalin, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Babadjanova, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantelejeva, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abramova, L. I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiganov, A. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polonikov, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khusnutdinova, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alda, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cruceanu, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouleau, G. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turecki, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laprise, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rivas, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayoral, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kogevinas, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grigoroiu-Serbanescu, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Propping, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cichon, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schratt, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, M. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-387159
DOI: 10.1038/tp.2015.159
Journal or Publication Title: Transl. Psychiatr.
Volume: 5
Date: 2015
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2158-3188
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MAJOR DEPRESSION; HOST GENES; ASSOCIATION; IDENTIFICATION; SCHIZOPHRENIA; BRAIN; BIOGENESIS; TRANSCRIPTOME; ARCHITECTURE; INDIVIDUALSMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38715

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