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Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11

Academic Article
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Overview

authors

  • Francks, C.
  • DeLisi, L. E.
  • Shaw, S. H.
  • Fisher, S. E.
  • Richardson, A. J.
  • Stein, J. F.
  • Monaco, A. P.

publication date

  • December 2003

journal

  • Human Molecular Genetics  Journal

abstract

  • Schizophrenia and non-right-handedness are moderately associated, and both traits are often accompanied by abnormalities of asymmetrical brain morphology or function. We have found linkage previously of chromosome 2p12-q11 to a quantitative measure of handedness, and we have also found linkage of schizophrenia/schizoaffective disorder to this same chromosomal region in a separate study. Now, we have found that in one of our samples (191 reading-disabled sibling pairs), the relative hand skill of siblings was correlated more strongly with paternal than maternal relative hand skill. This led us to re-analyse 2p12-q11 under parent-of-origin linkage models. We found linkage of relative hand skill in the RD siblings to 2p12-q11 with P=0.0000037 for paternal identity-by-descent sharing, whereas the maternally inherited locus was not linked to the trait (P>0.2). Similarly, in affected-sib-pair analysis of our schizophrenia dataset (241 sibling pairs), we found linkage to schizophrenia for paternal sharing with LOD=4.72, P=0.0000016, within 3 cM of the peak linkage to relative hand skill. Maternal linkage across the region was weak or non-significant. These similar paternal-specific linkages suggest that the causative genetic effects on 2p12-q11 are related. The linkages may be due to a single maternally imprinted influence on lateralized brain development that contains common functional polymorphisms.

subject areas

  • Chromosome Mapping
  • Chromosomes, Human, Pair 2
  • Female
  • Functional Laterality
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Lod Score
  • Male
  • Schizophrenia
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Identity

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddg362

PubMed ID

  • 14583442
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Additional Document Info

start page

  • 3225

end page

  • 3230

volume

  • 12

issue

  • 24

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