Schizophrenia: A genome scan targets chromosomes 3p and 8p as potential sites of susceptibility genes

A. E. Pulver, V. K. Lasseter, L. Kasch, P. Wolyniec, G. Nestadt, J. L. Blouin -, M. Kimberland, R. Babb, S. Vourlis, H. Chen, M. Lalioti, M. A. Morris, M. Karayiorgou, J. Ott, D. Meyers, S. E. Antonarakis, D. Housman, H. H. Kazazian

Research output: Contribution to journalArticlepeer-review

Abstract

Using a systematically ascertained sample of 57 families, each having 2 or more members with a consensus diagnosis of schizophrenia (DSM-III-R criteria), we have carried out linkage studies of 520 loci, covering approximately 70% of the genome for susceptibility loci for schizophrenia. A two-stage strategy based on lod score thresholds from simulation studies of our sample identified regions for further exploration. In each region, a dense map of highly informative dinucleotide repeat polymorphisms (heterozygosity greater than .70) was analyzed using dominant, recessive, and 'affected only' models and nonparametric sib pair identity-by-descent methods. For one region, 8p22-p21, affected sib-pair analyses gave a P value = .0001, corresponding to a lod score approximately equal to 3.00. For 8p22- p21, the maximum two-point lod score occurred using the 'affected only' recessive model (Z(MAX) = 2.35; θ(M) = θ(F)); allowing for a constant sex difference in recombination fractions found in reference pedigrees, Z(MAX) = 2.78 (θ(M)/θ(F) = 3). For a second region, 3p26-p24, the maximum two-point lod score was 2.34 ('affected only' dominant model), and the affected sib- pair P value was .01. These two regions are worthy of further exploration as potential sites of susceptibility genes for schizophrenia.

Original languageEnglish (US)
Pages (from-to)252-260
Number of pages9
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume60
Issue number3
DOIs
StatePublished - 1995

Keywords

  • dinucleotide
  • linkage
  • sib pair
  • systematic sample

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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