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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F15%3A43914870" target="_blank" >RIV/00023752:_____/15:43914870 - isvavai.cz</a>

Result on the web

<a href="http://www.nature.com/tp/journal/v5/n11/full/tp2015159a.html" target="_blank" >http://www.nature.com/tp/journal/v5/n11/full/tp2015159a.html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/tp.2015.159" target="_blank" >10.1038/tp.2015.159</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FL - Psychiatry, sexology

OECD FORD branch

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Project

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Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Translational Psychiatry

ISSN

2158-3188

e-ISSN

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Volume of the periodical

5

Issue of the periodical within the volume

10 November

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

"e678"

UT code for WoS article

000367665800004

EID of the result in the Scopus database

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