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Human Molecular Genetics Advance Access originally published online on October 28, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 24 3225-3230
DOI: 10.1093/hmg/ddg362
© 2003 Oxford University Press

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

Clyde Francks1,*, Lynn E. DeLisi2,3, Sarah H. Shaw4, Simon E. Fisher1, Alex J. Richardson5, John F. Stein5 and Anthony P. Monaco1

1Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK, 2Department of Psychiatry, New York University, New York, NY 10016, USA, 3The Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA, 4Illumina Inc., San Diego, CA 92121, USA and 5Department of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK

Received July 3, 2003; Revised September 29, 2003; Accepted October 20, 2003

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.

* To whom correspondence should be addressed. Tel: +44 1865287509; Fax: +44 1865287501; Email: clyde.francks{at}well.ox.ac.uk


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