Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia

Forstner, Andreas J. and Basmanav, F. Buket and Mattheisen, Manuel and Böhmer, Anne Christin and Hollegaard, Mads V. and Janson, Esther and Strengman, Eric and Priebe, Lutz and Degenhardt, Franziska and Hoffmann, Per and Herms, Stefan and Maier, Wolfgang and Mössner, Rainald and Rujescu, Dan and Ophoff, Roel A. and Moebus, Susanne and Mortensen, Preben Bo and Borglum, A. D. and Hougaard, David M. and Frank, Josef and Witt, Stephanie H. and Rietschel, Marcella and Zimmermann, Andrea and Nöthen, Markus M. and Miro, Xavier and Cichon, Sven. (2014) Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia. Journal of psychiatry & neuroscience, 39 (6). pp. 386-396.

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Official URL: https://edoc.unibas.ch/61544/

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BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder of unclear etiology. The strongest known genetic risk factor is the 22q11.2 microdeletion. Research has yet to confirm which genes within the deletion region are implicated in schizophrenia. The minimal 1.5 megabase deletion contains MIR185, which encodes microRNA 185. METHODS: We determined miR-185 expression in embryonic and adult mouse brains. Common and rare variants at this locus were then investigated using a human genetics approach. First, we performed gene-based analyses for MIR185 common variants and target genes using Psychiatric Genomics Consortium genome-wide association data. Second, MIR185 was resequenced in German patients (n = 1000) and controls (n = 500). We followed up promising variants by genotyping an additional European sample (patients, n = 3598; controls, n = 4082). RESULTS: In situ hybridization in mice revealed miR-185 expression in brain regions implicated in schizophrenia. Gene-based tests revealed association between common variants in 3 MIR185 target genes (ATAT1, SH3PXD2A, NTRK3) and schizophrenia. Further analyses in mice revealed overlapping expression patterns for these target genes and miR-185. Resequencing identified 2 rare patient-specific novel variants flanking MIR185. However, follow-up genotyping provided no further evidence of their involvement in schizophrenia. LIMITATIONS: Power to detect rare variant associations was limited. CONCLUSION: Human genetic analyses generated no evidence of the involvement of MIR185 in schizophrenia. However, the expression patterns of miR-185 and its target genes in mice, and the genetic association results for the 3 target genes, suggest that further research into the involvement of miR-185 and its downstream pathways in schizophrenia is warranted.
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:Canadian Medical Association
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:20 Jul 2020 12:56
Deposited On:20 Jul 2020 12:56

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