LiveZilla Live Chat Software

Constellation, le dépôt institutionnel de l'Université du Québec à Chicoutimi

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

Forstner A J, Hofmann A, Maaser A, Sumer S, Khudayberdiev S, Mühleisen 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, Müller-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 Grant 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 Catherine, Rivas F, Mayoral F, Kogevinas M, Grigoroiu-Serbanescu M, Propping P, Becker T, Rietschel M, Cichon S, Schratt G et Nöthen Markus M.. (2015). Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder. Translational Psychiatry, 5, (11), e678.

[img]
Prévisualisation
PDF - Version publiée
Disponible sous licence Creative Commons Attribution Non-commercial No Derivatives.

1MB

URL officielle: http://dx.doi.org/doi:10.1038/tp.2015.159

Résumé

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.

Type de document:Article publié dans une revue avec comité d'évaluation
ISSN:2158-3188
Volume:5
Numéro:11
Pages:e678
Version évaluée par les pairs:Oui
Date:2015
Identifiant unique:10.1038/tp.2015.159
Sujets:Sciences de la santé > Sciences médicales > Biologie moléculaire
Sciences de la santé > Sciences médicales > Génétique
Sciences de la santé > Sciences médicales > Psychiatrie
Département, module, service et unité de recherche:Départements et modules > Département des sciences fondamentales
Mots-clés:Bipolar disorder, molecular genetic, genetics, microRNAs
Déposé le:03 févr. 2016 00:49
Dernière modification:05 déc. 2016 20:51
Afficher les statistiques de telechargements

Éditer le document (administrateurs uniquement)

Creative Commons LicenseSauf indication contraire, les documents archivés dans Constellation sont rendus disponibles selon les termes de la licence Creative Commons "Paternité, pas d'utilisation commerciale, pas de modification" 2.5 Canada.

Bibliothèque Paul-Émile-Boulet, UQAC
555, boulevard de l'Université
Chicoutimi (Québec)  CANADA G7H 2B1
418 545-5011, poste 5630