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Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets

Molecular Psychiatry volume 18, pages 11–12 (2013)Cite this article

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A recently completed genome-wide association study (GWAS) implicated single-nucleotide polymorphisms in the MIR137 gene as being highly associated with schizophrenia.1 MIR137 encodes for the microRNA miR-137, which has been implicated in the regulation of adult neurogenesis2 and neuron maturation.3 Strikingly, four predicted targets of miR-137 also achieved genome-wide significance. These findings suggest that the dysregulation or dysfunction of miR-137 may be a novel pathological pathway underlying the etiology of schizophrenia. In this work, we use a luciferase-based reporter assay to demonstrate the site-specific regulation of CSMD1, C10orf26, CACNA1C and TCF4 by miR-137.

Schizophrenia is a spectrum disorder that has a lifetime prevalence of ∼1%. Disease onset usually occurs during adolescence, and suicide is the leading cause of premature death. Although monozygotic twin studies have clearly shown a genetic basis for this disease, the underlying genetics of schizophrenia have been difficult to delineate. A linkage study of a Scottish family with a high incidence of psychiatric disorders identified a rare, but highly penetrant, mutation in disrupted in schizophrenia-1 (DISC1);4 however, single-gene mutations have not been found in the vast majority of schizophrenia patients. It is believed that the onset of schizophrenia is due to the accumulation of several gene mutations, each of which has modest phenotypic effects, which are compounded with environmental factors. This complexity has made the identification of contributing genes difficult. Improvements in genotyping technology have allowed for GWAS in large patient populations. However, the results of schizophrenia GWASs have yet to be validated biologically.

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Authors and Affiliations

  1. Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA

    E Kwon, W Wang & L-H Tsai

  2. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA

    L-H Tsai

  3. Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA

    L-H Tsai

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  1. E Kwon
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  2. W Wang
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  3. L-H Tsai
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Correspondence to L-H Tsai.

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Kwon, E., Wang, W. & Tsai, LH. Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets. Mol Psychiatry 18, 11–12 (2013). https://doi.org/10.1038/mp.2011.170

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