Human Molecular Genetics Advance Access published online on October 28, 2003
Human Molecular Genetics, doi:10.1093/hmg/ddg362
© 2003 by Oxford University Press
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1 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, United Kingdom
* To whom correspondence should be addressed. E-mail: clyde.francks{at}well.ox.ac.uk.
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 centimorgans 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 lateralised brain development that contains common functional polymorphisms.
Article
Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11
2 Department of Psychiatry, New York University, New York 10016, USA; The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA
3 Illumina Inc., San Diego, CA 92121, USA
4 Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
5 Department of Physiology, University of Oxford, Parks Road, Oxford, OX1 3PT, UK
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