An affected sib pair study for schizophrenia on the X chromosome

As part of a systematic two stage genome scan for schizophrenia susceptibility genes, we genotyped nine microsatellites covering chromosome X at an average density of 20 cM through 97 affected sib pairs. For linkage analysis, the sample was stratified and lod scores calculated separately for male-male (M-M), male-female (M-F), and female-female (F-F) pairs, then combined to give an overall result. Stage 1 produced maximum lod scores of 0.9 at DXS1214 in M-M pairs and 1.1 at DXS993 in F-F pairs that increased to 1.5 for the combined sample. In stage 2, 17 markers spanning the regions of interest at an average density of 10 cM were genotyped in our full sample of 197 sib pairs. Markers within the MAO-A and androgen receptor genes were also included in this stage. Maximum lod scores of 1.9 at DXS993 and 1.7 at DXS8092 were observed in the M-M pairs. No excess sharing was seen in the mixed sex and F-F pairs. Our results define a 50 cM region of interest spanning the centromere and encompassing the region previously implicated by DeLisi et al. [1994].1 It is unclear why such a pattern of sharing between M-M pairs only should occur, and further analysis of this region is needed.