Linkage analysis of candidate genes as susceptibility loci for osteoarthritis - suggestive linkage of COL9A1 to female hip osteoarthritis

Objective. To examine 11 candidate genes as susceptibility loci for osteoar thritis (OA). Methods. A total of 481 families have been ascertained in which at least tw o siblings have had joint replacement surgery of the hip, or knee, or hip a nd knee for idiopathic OA. Each candidate gene was targeted using one or mo re intragenic or closely linked microsatellite marker. The linkage data wer e analysed unstratified and following stratification by sex and by joint re placed (hip or knee). Results. The analyses revealed suggestive linkage of the type IX collagen g ene COL9A1 (6q12-q13) to a subset of 132 families that contained affected f emales who were concordant for hip OA (female-hip) with a P-value of 0.0005 3 and logarithm of the odds (LOD) score of 2.33 [corrected P-value of 0.001 6, corrected LOD score of 1.85]. Conclusions. COL9A1 may therefore be a susceptibility locus for female hip OA. In addition, there was weak evidence of linkage to HLA/COL11A2 (6p21.3) in female hip OA with a corrected P-value of 0.016.