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Article
Nature Genetics  11, 287 - 293 (1995)
doi:10.1038/ng1195-287

A potential vulnerability locus for schizophrenia on chromosome 6p24−22: evidence for genetic heterogeneity

Richard E. Straub1, Charles J. MacLean1, 2, F. Anthony O'Neill3, John Burke4, 5, Bernadette Murphy4, Fiona Duke3, Rosemarie Shinkwin4, Bradley T. Webb1, Jie Zhang1, Dermot Walsh4 & Kenneth S. Kendler1, 2

  1Department of Psychiatry, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA

  2Department of Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA

  3The Department of Psychiatry, The Queens University, Belfast, Northern Ireland, UK

  4The Health Research Board, Dublin, Ireland

  5Current address: Department of Psychiatry, University of Leicester, UK

 Correspondence should be addressed to K.S.K.

In 265 Irish pedigrees, with linkage analysis we find evidence for a vulnerability locus for schizophrenia in region 6p24−22. The greatest lod score, assuming locus heterogeneity, is 3.51 (P = 0.0002) with D6S296. Another test, the C test, also supported linkage, the strongest results being obtained with D6S296 (P = 0.00001), D6S274 (P = 0.004) and D6S285 (P = 0.006). Non−parametric analysis yielded suggestive, but substantially weaker, findings. This locus appears to influence the vulnerability to schizophrenia in roughly 15 to 30% of our pedigrees. Evidence for linkage was maximal using an intermediate phenotypic definition and declined when this definition was narrowed or was broadened to include other psychiatric disorders.

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