Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females

Authors

  • Mary Perrin,

    Corresponding author
    1. Department of Psychiatry, New York University School of Medicine, New York, New York
    2. Department of Environmental Medicine, New York University School of Medicine, New York, New York
    • Department of Psychiatry and Environmental Medicine, 550 First Avenue, NBV 22N10, New York University School of Medicine, New York, NY 10016.
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  • Susan Harlap,

    1. Department of Psychiatry, New York University School of Medicine, New York, New York
    2. Department of Environmental Medicine, New York University School of Medicine, New York, New York
    3. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York
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  • Karine Kleinhaus,

    1. Department of Psychiatry, New York University School of Medicine, New York, New York
    2. Department of Environmental Medicine, New York University School of Medicine, New York, New York
    3. Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York
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  • Pesach Lichtenberg,

    1. Hebrew University, Jerusalem, Israel
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  • Orly Manor,

    1. Hebrew University, Jerusalem, Israel
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  • Benjamin Draiman,

    1. Hebrew University, Jerusalem, Israel
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  • Shmuel Fennig,

    1. Shalvata Mental Health Center, Jerusalem, Israel
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  • Dolores Malaspina

    1. Department of Psychiatry, New York University School of Medicine, New York, New York
    2. Department of Environmental Medicine, New York University School of Medicine, New York, New York
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  • Please cite this article as follows: Perrin M, Harlap S, Kleinhaus K, Lichtenberg P, Manor O, Draiman B, Fennig S, Malaspina D. 2010. Older Paternal Age Strongly Increases the Morbidity for Schizophrenia in Sisters of Affected Females. Am J Med Genet Part B 153B:1329–1335.

  • This research was performed at New York University, New York, New York and Hebrew University and Shalvata Mental Health Center Jerusalem, Israel.

Abstract

The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers ≥35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9–19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7–6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6–6.6) and younger fathers (RR = 1.6, 95% CI 0.7–3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations. © 2010 Wiley-Liss, Inc.

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