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Genetic variation in the miR-708 gene and its binding targets in bipolar disorder

Fiorentino, A; O'Brien, NL; Sharp, SI; Curtis, D; Bass, NJ; McQuillin, A; (2016) Genetic variation in the miR-708 gene and its binding targets in bipolar disorder. Bipolar Disorders , 18 (8) pp. 650-656. 10.1111/bdi.12448. Green open access

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Abstract

OBJECTIVE: rs12576775 was found to be associated with bipolar disorder (BD) in a genome-wide association study (GWAS). The GWAS signal implicates genes for the microRNAs miR-708 and miR-5579 and the first exon of the Odd Oz/ten-m homolog 4 gene (ODZ4). In the present study, miR-708, its surrounding region, and its targets were analyzed for potential BD-associated functional variants. METHODS: The miR-708 gene and surrounding regions were screened for variation using high-resolution melting (HRM) analysis in 1099 cases of BD, followed by genotyping of rare variants in an enlarged sample of 2078 subjects with BD, 1303 subjects with schizophrenia, and 1355 healthy controls. Whole-genome sequencing data from 99 subjects with BD were analyzed for variation in potential miR-708 binding sites. The minor allele frequencies (MAFs) of these variants were compared with those reported in reference individuals. RESULTS: Three variants detected by HRM were selected to be genotyped. rs754333774 was detected in three cases of BD, two cases of schizophrenia, and no controls. This variant is located 260 base pairs upstream from miR-708 and may play a role in controlling the expression of the miR. Four variants were identified in miR-708 targets binding sites. The MAFs of each of these variants were similar in BD and reference samples. CONCLUSIONS: We report a single recurrent variant located near the miR-708 gene that may have a role in BD and schizophrenia susceptibility. These findings await replication in independent cohorts, as do functional analyses of the potential consequences of this variant.

Type: Article
Title: Genetic variation in the miR-708 gene and its binding targets in bipolar disorder
Location: Denmark
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bdi.12448
Publisher version: http://doi.org/10.1111/bdi.12448
Language: English
Additional information: © 2016 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Bipolar disorder, miR-708, microRNA, sequencing, susceptibility, variation
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/1529983
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