Sex differences in the genetic risk for schizophrenia: History of the evidence for sex-specific and sex-dependent effects

Authors

  • Jill M. Goldstein,

    Corresponding author
    1. Brigham & Women's Hospital Departments of Psychiatry and Medicine, Division of Women's Health, Connors Center for Women's Health & Gender Biology, Boston, Massachusetts
    2. Departments of Psychiatry and Medicine, Harvard Medical School, Boston, Massachusetts
    3. Division of Psychiatric Neuroscience, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
    • Correspondence to:

      Jill M. Goldstein, Ph.D., Brigham and Women's Hospital, One Brigham Circle, Division of Women's Health, 1620 Tremont Street, 3rd Floor, Boston, MA 02120, USA. E-mail: jill_goldstein@hms.harvard.edu

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  • Sara Cherkerzian,

    1. Brigham & Women's Hospital Departments of Psychiatry and Medicine, Division of Women's Health, Connors Center for Women's Health & Gender Biology, Boston, Massachusetts
    2. Departments of Psychiatry and Medicine, Harvard Medical School, Boston, Massachusetts
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  • Ming T. Tsuang,

    1. Division of Psychiatric Neuroscience, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts
    2. Division of Public Psychiatry, Beth Israel Deaconess Hospital, Massachusetts Mental Health Center and Harvard Medical School, Boston, Massachusetts
    3. Department of Psychiatry, Center for Behavior Genomics, University of California at San Diego, San Diego, California
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  • Tracey L. Petryshen

    1. Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts
    2. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
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Abstract

Although there is a long history to examinations of sex differences in the familial (and specifically, genetic) transmission of schizophrenia, there have been few investigators who have systematically and rigorously studied this issue. This is true even in light of population and clinical studies identifying significant sex differences in incidence, expression, neuroanatomic and functional brain abnormalities, and course of schizophrenia. This review highlights the history of work in this arena from studies of family transmission patterns, linkage and twin studies to the current molecular genetic strategies of large genome-wide association studies. Taken as a whole, the evidence supports the presence of genetic risks of which some are sex-specific (i.e., presence in one sex and not the other) or sex-dependent (i.e., quantitative differences in risk between the sexes). Thus, a concerted effort to systematically investigate these questions is warranted and, as we argue here, necessary in order to fully understand the etiology of schizophrenia. © 2013 Wiley Periodicals, Inc.

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