A re-review of the association between the NOTCH4 locus and schizophrenia

Authors

  • Christina Shayevitz,

    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry & Behavioral Sciences and Neuroscience & Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Ori S. Cohen,

    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry & Behavioral Sciences and Neuroscience & Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Stephen V. Faraone,

    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry & Behavioral Sciences and Neuroscience & Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
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  • Stephen J. Glatt

    Corresponding author
    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Departments of Psychiatry & Behavioral Sciences and Neuroscience & Physiology, Medical Genetics Research Center, SUNY Upstate Medical University, Syracuse, New York
    • SUNY Upstate Medical University, 750 East Adams Street, Weiskotten Hall, Room 3283, Syracuse, NY 13210.
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  • How to Cite this Article: Shayevitz C, Cohen OS, Faraone SV, Glatt SJ. 2012. A Re-Review of the Association Between the NOTCH4 Locus and Schizophrenia. Am J Med Genet Part B 159B:477–483.

Abstract

NOTCH4 has long been identified as a candidate susceptibility gene for schizophrenia, but the collective body of genetic association studies of this gene has been less than conclusive. Recently a variant in NOTCH4 was implicated as one of the most reliably associated polymorphisms observed in a genome-wide association scan of the disorder, and the collective evidence for this polymorphism now surpasses criteria for genome-wide significance. To place these developments in context, we now summarize the initial work identifying NOTCH4 as a candidate gene for schizophrenia. The results of the genome-wide association studies that have confirmed this as a risk gene, and novel bioinformatics analyses that reveal potential functional profiles of the most likely risk-conferring polymorphisms. These analyses suggest that the NOTCH4 polymorphisms most strongly associated with schizophrenia exert their effects on susceptibility by altering the efficiency and/or alternative splicing of Notch4 transcripts. Further experimental evidence should be pursued to clarify the NOTCH4-regulated molecular and cellular phenotypes of relevance to the disorder, and the functional consequences of the implicated polymorphisms in the gene. © 2012 Wiley Periodicals, Inc.

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