Genetic heterogeneity in schizophrenia: Stratification of genome scan data using co-segregating related phenotypes

A. E. Pulver, J. Mulle, G. Nestadt, K. L. Swartz, J. L. Blouin, B. Dombroski, K. Y. Liang, D. E. Housman, H. H. Kazazian, S. E. Antonarakis, V. K. Lasseter, P. S. Wolyniec, M. H. Thornquist, J. A. McGrath

Research output: Contribution to journalArticle

Abstract

Despite considerable effort to identify susceptibility loci for schizophrenia, none have been localized. Multiple genome scans and collaborative efforts have shown evidence for linkage to regions on chromosomes 1q, 5q, 6q, 8p, 13q, 10p and 22q.1-9 Heterogeneity is likely. We previously mapped schizophrenia susceptibility loci (SSL) to chromosomes 13q32 (P = 0.00002) and 8p21-22 (P = 0.0001) using 54 multiplex pedigrees and suggested linkage heterogeneity. We have now stratified these families based on co-segregating phenotypes in nonschizophrenic first degree relatives (schizophrenia spectrum personality disorders (SSPD); psychotic affective disorders (PAD)). Genome scans were conducted for these phenotypic subgroups of families and broadened affected phanotypes were tested. The SSPD group provided its strongest genome-wide linkage support for the chromosome 8p21 region (D8S1771) using either narrow (non-parametric lod (NPL) P = 0.000002) or broadened phenotypes (NPL P = 0.0000008) and a new region of interest on 1p was identified (P = 0.006). For PAD families, the peak NPL in the genome scan occurred on chromosome 3p26-p24 (P = 0.008). The identification of multiple susceptibility loci for schizophrenia may be enhanced by stratification of families using psychiatric diagnoses of the non-schizophrenic relatives.

Original languageEnglish (US)
Pages (from-to)650-653
Number of pages4
JournalMolecular psychiatry
Volume5
Issue number6
DOIs
StatePublished - Jan 1 2000

Keywords

  • 13q
  • 8p
  • Genetics
  • Heterogeneity
  • Linkage
  • Schizophrenia
  • Spectrum personality disorders

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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  • Cite this

    Pulver, A. E., Mulle, J., Nestadt, G., Swartz, K. L., Blouin, J. L., Dombroski, B., Liang, K. Y., Housman, D. E., Kazazian, H. H., Antonarakis, S. E., Lasseter, V. K., Wolyniec, P. S., Thornquist, M. H., & McGrath, J. A. (2000). Genetic heterogeneity in schizophrenia: Stratification of genome scan data using co-segregating related phenotypes. Molecular psychiatry, 5(6), 650-653. https://doi.org/10.1038/sj.mp.4000814