Parent-of-origin effects on handedness and schizophrenia susceptibility on chromosome 2p12-q11.
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.
Francks
Clyde
C
Wellcome Trust Centre for Human Genetics, University of Oxford, UK. clyde.francks@well.ox.ac.uk
DeLisi
Lynn E
LE
Shaw
Sarah H
SH
Fisher
Simon E
SE
Richardson
Alex J
AJ
Stein
John F
JF
Monaco
Anthony P
AP
D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D005260:Female; D007839:Functional Laterality / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008126:Lod Score; D008297:Male; D012559:Schizophrenia / Q000235:genetics*