Generalized OA (GOA) is a well-characterized subset of primary OA which is strongly associated with the occurrence of Heberden's nodes. Using gene-specific highly polymorphic markers and affected sib pair (ASP) analyses, we have investigated genetic linkage between GOA and three cartilage matrix genes: COL2A1 which encodes type II collagen; CRTL1 which encodes the cartilage link protein and CRTM which encodes the cartilage matrix protein. The analyses showed no linkage between GOA and the three genes in the 38 sib pairs examined. Since we examined a relatively modest number of sib pairs, our results can only exclude COL2A1, CRTL1 and CRTM as major susceptibility loci for GOA.