Transmission of a psychometric indicator for liability to schizophrenia in normal families

Authors

  • Dr. Steven O. Moldin,

    Corresponding author
    1. Department of Psychiatry, Washington University School of Medicine, St. Louis
    2. Jewish Hospital of St. Louis, St. Louis
    • Department of Psychiatry, Jewish Hospital of St. Louis, 216 S. Kingshighway Blvd., St. Louis, MO 63110

    Search for more papers by this author
  • John P. Rice,

    1. Department of Psychiatry, Washington University School of Medicine, St. Louis
    2. Division of Biostatistics, Washington University School of Medicine, St. Louis
    3. Jewish Hospital of St. Louis, St. Louis
    Search for more papers by this author
  • Irving I. Gottesman,

    1. Department of Psychology, University of Virginia, Charlottesville
    Search for more papers by this author
  • L. Erlenmeyer-Kimling,

    1. Department of Psychiatry and of Genetics and Development, Columbia University College of Physicians and Surgeons and Division of Developmental Behavioral Studies, Department of Medical Genetics, New York State Psychiatric Institute, New York
    Search for more papers by this author
  • C. F. Sing

    EditorSearch for more papers by this author

Abstract

The genetic analysis of schizophrenia would be facilitated by identification of a heritable correlate of liability. Deviance on an index of Minnesota Multiphasic Personality Inventory (MMPI) signs is associated with the disease phenotype; the familial aggregation and mode of transmission of this continuous psychometric indicator have yet to be established. In this paper, we examine the indicator through commingling analysis and segregation analysis with both the mixed and unified models on 65 nuclear families containing 211 normal individuals. Evidence for a high degree of familiality is found. Analysis of untransformed data under a conditional likelihood provides evidence for Mendelian transmission of a major gene with commingling of two distributions. The frequency of the “high index score” allele is 0.15, with the gene accounting for 31% of the total population variance; such a locus would be relevant to the study of psychopathology as 28% of the population would carry at least one deviant allele. When power-transformed scores are used to eliminate skewness, there is evidence for one distribution and it is not possible to distinguish single gene from multifactorial (polygenic or cultural) inheritance. While our findings regarding mode of transmission must be interpreted cautiously and confirmation of a single locus requires further study, demonstration of familiality warrants continued investigation of the index as an indicator of liability for schizophrenia.

Ancillary