Initially, genetic linkage analysis (Box 1) is performed to identify the many different QTLs that regulate various arthritis phenotypes, including disease onset and severity, and also subphenotypes, such as CD4:CD8 T-cell ratio, and the presence of α­1-acid glycoprotein (a marker of the systemic inflammatory response) and of cartilage oligomeric matrix protein (a marker of cartilage destruction) (Kawahito et al., 1998; Lorentzen et al., 1998; Olofsson et al., 2003b; Remmers et al., 1996). This evidence concerns the gene COMP and Arthritis.