Osteoarthritis-susceptibility locus on chromosome 11q, detected by linkage

We present a two-stage genomewide scan for osteoarthritis-susceptibility lo ci, using 481 families that each contain at least one affected sibling pair . The first stage, with 272 microsatellite markers and 297 families, involv ed a sparse map covering 23 chromosomes at intervals of similar to 15 cM. S ixteen markers that showed evidence of linkage at nominal P less than or eq ual to .05 were then taken through to the second stage, with an additional 184 families. This second stage confirmed evidence of linkage for markers o n chromosome 11q. Additional markers from this region were then typed to cr eate a denser map. We obtained a maximum single-point LOD score, at D11S901 , of 2.40 (P = .0004) and a maximum multipoint-LOD score of 3.15, between m arkers D11S1358 and D11S35. A subset of 196 of the 481 families, comprising affected female sibling pairs, generated a corrected LOD score of 2.54 (P = .0003) for marker D11S901, with evidence for linkage extending 12 cM prox imal to this marker. When we stratified for affected male sibling pairs the re was no evidence of linkage to chromosome 11. Our data suggest that a fem ale-specific susceptibility gene for idiopathic osteoarthritis is located o n chromosome 11q.