title: Transcriptional consequences of schizophrenia candidate miR-137 manipulation in human neural progenitor cells.
abstract: MIR137, transcribed as the microRNA miR-137, is one of the leading candidate schizophrenia susceptibility genes to arise from large genome-wide association studies (GWAS) of the disorder. Recent data suggest that miR-137 modulates the expression of other schizophrenia susceptibility genes. Although bioinformatic resources are available with which to predict genes regulated by individual microRNA, there has been a lack of empirical data on genome-wide gene expression changes following miR-137 manipulation. We have therefore performed a genome-wide assessment of transcriptional changes in a human neural progenitor cell line after miR-137 over-expression and inhibition in order to elucidate molecular pathways by which genetic perturbation of miR-137 could promote susceptibility to schizophrenia. Bioinformatically-predicted miR-137 targets showed a small but highly significant down-regulation following miR-137 over-expression. Genes that were significantly down-regulated in association with miR-137 over-expression were enriched for involvement in neuronal differentiation. Differentially expressed genes that were confirmed by qPCR included others at genome-wide significant risk loci for schizophrenia (MAD1L1 and DPYD) and BDNF. These data point to molecular pathways through which genetic variation at the MIR137 locus could confer risk for schizophrenia.
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hill
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Jacek G
authors.initials: JG
authors.lastname: Donocik
authors.affiliation: The Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
authors.forename: Rosamond A
authors.initials: RA
authors.lastname: Nuamah
authors.affiliation: The Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Sainz-Fuertes
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, King's College London, London, UK. Electronic address: nicholas.bray@kcl.ac.uk.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bray
mesh_terms: D002277:Carcinoma / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D019295:Computational Biology; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics*; D059467:Transcriptome; D014162:Transfection
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs
keywords: GWAS; Gene expression; MIR137; MicroRNA; Pathway; Schizophrenia; miR-137