Significant evidence for a schizophrenia susceptibility locus in the centromeric region of human chromosome

Sarah H. Shaw, Gail Shields, Angela B. Smith, Veronica W. Larach, Nigel Wellman, Josephine Loftus, Betsy Nanthankumar, Kamran Razi, John Stewart, Margherita Comazzi, Antonio Vita, Thomas Heffner, Robin Sherrington, Timothy J. Crow, Lynn E. DeLisi

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We have recently completed a genome-wide search for schizophrenia susceptibility genes in a collection of 301 pedigrees resulting in one significant (lod = 3.6, 10p14) and two suggestive (2cen, lod = 2.9; 3q27, lod = 2.3) linkage regions (DeLisi et al., submitted). As part of the schizophrenia genetics initiative, Faraone et al. (1998) reported linkage to markers in 2cen in a set of 43 pedigrees. In order to combine these results using the same genetic markers, analytic methods, and phenotypes, we have genotyped markers in a 40 cM region around the pericentromeric region of chromosome 2 in 42 NIMH pedigrees with at least 2 members diagnosed with schizophrenia from the schizophrenia. Both pedigree sets were combined together for a total of 343 pedigrees and the marker data were analyzed using both schizophrenia-only and schizophrenia plus schizoaffective disorder phenotypes. Multipoint non-parametric allele-sharing tests resulted in 2 peaks. Using a schizophrenia-only phenotype, a first peak occurred at D2S160 in 2q13 with a lod score of 5.4. A second peak occurred approximately 15 cM away at D2S139/D2S417 in 2p12 with a lod score of 4.0. The data were also analyzed using parametric methods and a schizophrenia-only phenotype using both dominant and recessive affecteds-only analyses. Tests under homogeneity resulted in a peak lod score of 3.8 at D2S160 using a dominant model (θ = 0.20). Under heterogeneity, the peak lod score increased to 4.0 at D2S160 (α = 0.40, θ = 0). In addition, several other markers in the 40 cM centromeric region of chromosome 2 had lod scores greater than 3. The data presented encompasses one of the largest pedigree collections for schizophrenia genetics studies and demonstrates highly significant results.

Original languageEnglish
Pages (from-to)563-564
Number of pages2
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number7
Publication statusPublished - 8 Oct 2001

ASJC Scopus subject areas

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


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