Linkage studies of schizophrenia: A simulation study of statistical power

Authors

  • Wei J. Chen,

    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Psychiatry Service, Brockton-West Roxbury Veterans Affairs Medical Center, Brockton, Massachusetts
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  • Stephen V. Faraone,

    1. Section of Psychiatric Epidemiology and Genetics, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    2. Psychiatry Service, Brockton-West Roxbury Veterans Affairs Medical Center, Brockton, Massachusetts
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  • Ming T. Tsuang M.D., Ph.D, D.Sc.,

    Corresponding author
    1. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
    2. Section of Psychiatric Epidemiology and Genetics, Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
    3. Psychiatry Service, Brockton-West Roxbury Veterans Affairs Medical Center, Brockton, Massachusetts
    • Psychiatry Service (116A), Veterans Affairs Medical Center, 940 Belmont Street, Brockton, MA 02401

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  • G. P. Vogler

    EditorSearch for more papers by this author

Abstract

In planning for a linkage study, it is important to determine the number of pedigrees needed to show linkage. Our study overcomes some of the limitations of previous power studies by simulating multigeneration pedigrees to be compatible with the demographic and genetic epidemiological features of schizophrenia; these are variable age at onset, reduced fertility, and increased mortality after onset. We evaluate the power of these pedigrees by first simulating an ascertainment rule requiring at least three ill family members per pedigree and then simulating the trait and marker genotypes according to a single gene model known to fit epidemiological family study data. Our analysis allows for incomplete and age-dependent penetrance, phenocopies, and interpedigree heterogeneity. We present the power to detect linkage at several lod score thresholds since the multiple tests and phenotypic models required for complex diseases may necessitate using a lod score significance level greater than three. The sample size needed to achieve sufficient power is feasible if 50% of the pedigrees are linked to the marker under test. It may not be feasible to detect linkage if only 25% of the pedigrees are linked, even if a very closely linked marker is used. Our results indicate that to be certain of adequate statistical power, linkage analyses of schizophrenia will require very large samples that do not have a marked degree of genetic heterogeneity. © 1992 Wiley-Liss, Inc.

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