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Similarities and differences in peripheral blood gene-expression signatures of individuals with schizophrenia and their first-degree biological relatives

Authors

  • Stephen J. Glatt,

    Corresponding author
    1. Psychiatric Genetic Epidemiology & Neurobiology Laboratory (PsychGENe Lab), Medical Genetics Research Center, Department of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, 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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  • William S. Stone,

    1. Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Harvard Institute of Psychiatric Epidemiology and Genetics, Department of Epidemiology and Psychiatry, Harvard School of Public Health and Harvard Medical School, Boston, Massachusetts
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  • Nadine Nossova,

    1. Research Department, GeneNews Ltd, Richmond Hill, Ontario, Canada
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  • Choong-Chin Liew,

    1. Research Department, GeneNews Ltd, Richmond Hill, Ontario, Canada
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  • Larry J. Seidman,

    1. Massachusetts Mental Health Center Public Psychiatry Division of the Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Harvard Institute of Psychiatric Epidemiology and Genetics, Department of Epidemiology and Psychiatry, Harvard School of Public Health and Harvard Medical School, Boston, Massachusetts
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  • Ming T. Tsuang

    1. Harvard Institute of Psychiatric Epidemiology and Genetics, Department of Epidemiology and Psychiatry, Harvard School of Public Health and Harvard Medical School, Boston, Massachusetts
    2. Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, La Jolla, California
    3. Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, California
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  • How to Cite this Article: Glatt SJ, Stone WS, Nossova N, Liew C-C, Seidman LJ, Tsuang MT. 2011. Similarities and differences in peripheral blood gene-expression signatures of individuals with schizophrenia and their first-degree biological relatives. Am J Med Genet Part B 156:869–887.

Abstract

Several studies have evaluated the potential utility of blood-based whole-transcriptome signatures as a source of biomarkers for schizophrenia. This endeavor has been complicated by the fact that individuals with schizophrenia typically differ from appropriate comparison subjects on more than just the presence of the disorder; for example, individuals with schizophrenia typically receive antipsychotic medications, and have been dealing with the sequelae of this chronic illness for years. The inability to control such factors introduces a considerable degree of uncertainty in the results to date. To overcome this, we performed a blood-based gene-expression profiling study of schizophrenia patients (n = 9) as well as their unmedicated, nonpsychotic, biological siblings (n = 9) and unaffected comparison subjects (n = 12). The unaffected biological siblings, who may harbor some of the genetic predisposition to schizophrenia, exhibited a host of gene-expression differences from unaffected comparison subjects, many of which were shared by their schizophrenic siblings, perhaps indicative of underlying risk factors for the disorder. Several genes that were dysregulated in both individuals with schizophrenia and their siblings related to nucleosome and histone structure and function, suggesting a potential epigenetic mechanism underlying the risk state for the disorder. Nonpsychotic siblings also displayed some differences from comparison subjects that were not found in their affected siblings, suggesting that the dysregulation of some genes in peripheral blood may be indicative of underlying protective factors. This study, while exploratory, illustrated the potential utility and increased informativeness of including unaffected first-degree relatives in research in pursuit of peripheral biomarkers for schizophrenia. © 2011 Wiley Periodicals, Inc.

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