An examination of linkage of schizophrenia and schizoaffective disorder to the pseudoautosomal region (Xp22.3)

We investigated linkage between schizophrenia and the loci DXYS14, DXYS17, and MIC2 within the pseudoautosomal region in 85 families with two or more siblings suffering from schizophrenia or schizoaffective disorder. A maximum lod score of 2.44 was reached at MIC2, with a dominant model of inheritance at a recombination fraction of 0.367 in females and 0.046 in males (a F:M sex ratio > 1, i.e. opposite to that expected with a pseudoautosomal locus). Evidence consistent with linkage (P = 0.01) was also obtained with a sibling pair analysis at the MIC2 locus. These data do not support (although they do not definitively exclude) a locus within the pseudoautosomal region; they are consistent with the presence of a gene that predisposes to schizophrenia in the sex-specific regions of the X and Y chromosomes.