Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia
| Autor: | Eric Strengman, Lutz Priebe, Marcella Rietschel, Anne C. Böhmer, David M. Hougaard, Xavier Miró, Stefan Herms, Andreas Zimmer, Roel A. Ophoff, Markus M. Nöthen, Josef Frank, F. B. Basmanav, Per Hoffmann, Dan Rujescu, Stephanie H. Witt, Franziska Degenhardt, Anders D. Børglum, Manuel Mattheisen, Sven Cichon, Rainald Mössner, Andreas J. Forstner, Preben Bo Mortensen, Wolfgang Maier, Susanne Moebus, Mads V. Hollegaard, Esther Janson |
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| Rok vydání: | 2014 |
| Předmět: |
Genotyping Techniques
Medizin Genome-wide association study Inbred C57BL Mice 0302 clinical medicine Heterocyclic Compounds 2.1 Biological and endogenous factors Pharmacology (medical) Aetiology In Situ Hybridization Genetics Psychiatry 0303 health sciences Brain Serious Mental Illness Research Papers 3. Good health Psychiatry and Mental health Mental Health trkC Microtubule Proteins Cognitive Sciences Receptor Biotechnology Clinical Sciences Genomics Locus (genetics) Biology White People 03 medical and health sciences Acetyltransferases Genetic variation Animals Humans Receptor trkC Genotyping Gene Biological Psychiatry 030304 developmental biology Genetic association Whites Human Genome Neurosciences Genetic Variation Human genetics Brain Disorders Mice Inbred C57BL MicroRNAs Schizophrenia 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Journal of psychiatry & neuroscience : JPN, vol 39, iss 6 Europe PubMed Central Forstner, A J, Basmanav, F B, Mattheisen, M, Böhmer, A C, Hollegaard, M V, Janson, E, Strengman, E, Priebe, L, Degenhardt, F, Hoffmann, P, Herms, S, Maier, W, Mössner, R, Rujescu, D, Ophoff, R A, Moebus, S, Mortensen, P B, Børglum, A D, Hougaard, D M, Frank, J, Witt, S H, Rietschel, M, Zimmer, A, Nöthen, M M, Miró, X, Cichon, S & GROUP Investigators 2014, ' Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia ', Journal of Psychiatry and Neuroscience, vol. 39, no. 6, pp. 386-396 . https://doi.org/10.1503/jpn.130189 |
| ISSN: | 1488-2434 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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