LINKAGE STUDY OF SCHIZOPHRENIA TO MARKERS WITHIN XP11 NEAR THE MAOB GENE

A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular geneti c studies produced weak evidence for linkage of schizophrenia to the p roximal short arm of the X-chromosome, while some other regions were n ot ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a materna l pattern of inheritance (Study I.); and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II.). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheri tance at a theta of 0.20) for locus DXS7, with scores below 0.50 for o ther markers in this region (MAOB, DXS228, and ARAF1). Significant all ele sharing among affected sibling pairs was present at DXS7. In the s econd study, positive lod scores were observed at MAOB (highest of 2.1 6 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for rece ssive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-c hromosome have been investigated without evidence for linkage being fo und, a locus predisposing to schizophrenia in the proximal short arm o f the X-chromosome is not excluded. (C) 1997 Elsevier Science Ireland Ltd.