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MicroRNAs in Copy Number Variants in Schizophrenia: Misregulation of Genome-wide Gene Expression Programs

  • Eric M. Morrow
    Correspondence
    Address correspondence to Eric M. Morrow, M.D., Ph.D., Brown University, Institute for Brain Science, Lab for Molecular Medicine, 70 Ship Street, Providence, RI 02912
    Affiliations
    Department of Molecular Biology, Cell Biology and Biochemistry and Institute for Brain Science, Brown University, Providence; and Developmental Disorders Genetics Research Program, Emma Pendleton Bradley Hospital, and the Department of Psychiatry and Human Behavior, Brown University Medical School, East Providence, Rhode Island.
    Search for articles by this author
      The study by Warnica et al. (
      • Warnica W.
      • Merico D.
      • Costain G.
      • Alfred S.E.
      • Wei J.
      • Marshall C.R.
      • et al.
      Copy number variable microRNAs in schizophrenia and their neurodevelopmental gene targets.
      ) investigates a clever and straightforward idea. Of course, there is substantial evidence to support the role of rare genomic copy number variants (CNVs) in schizophrenia and other neuropsychiatric disease (
      • Morrow E.M.
      Genomic copy number variation in disorders of cognitive development.
      ). A role for specific microRNA pathways (miRNAs) in schizophrenia has also been convincingly demonstrated in a variety of ways (
      Schizophrenia Psychiatric Genome-Wide Association Study Consortium
      Genome-wide association study identifies five new schizophrenia loci.
      ,

      Xu B, Hsu PK, Karayiorgou M, Gogos J (2012): MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction. Neurobiol Dis 46:291–301.

      ). For example, the well-known schizophrenia-associated deletion at 22q11.2 includes both miR-185 as well as the gene DGCR8, a component of the microprocessor complex that is involved in the initial step of miRNA biogenesis. Warnica et al. (
      • Warnica W.
      • Merico D.
      • Costain G.
      • Alfred S.E.
      • Wei J.
      • Marshall C.R.
      • et al.
      Copy number variable microRNAs in schizophrenia and their neurodevelopmental gene targets.
      ) have now conducted a genome-wide test to determine if rare CNVs are enriched for miRNA loci. Their results demonstrate that this is indeed the case, and they further attempt to map the putative targets of these miRNAs in an effort to uncover molecular mechanisms in the disorder.
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      References

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        • Merico D.
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        • Wei J.
        • Marshall C.R.
        • et al.
        Copy number variable microRNAs in schizophrenia and their neurodevelopmental gene targets.
        Biol Psychiatry. 2015; 77: 158-166
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        Genomic copy number variation in disorders of cognitive development.
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        • Schizophrenia Psychiatric Genome-Wide Association Study Consortium
        Genome-wide association study identifies five new schizophrenia loci.
        Nat Genet. 2011; 43: 969-976
      1. Xu B, Hsu PK, Karayiorgou M, Gogos J (2012): MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction. Neurobiol Dis 46:291–301.

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