Susceptibility genes for rheumatoid arthritis - a rapidly expanding harvest.

In addition to the HLA locus, over 30 genetic loci have been convincingly associated with risk for rheumatoid arthritis, and the majority of these associations have been identified in the last four years. Although this is a remarkable accomplishment, the majority of the genetic risk for RA still remains to be identified. Some of this "missing heritability" will likely be due to rare genetic variation, and will require extensive resequencing of the genomes of patients with RA. In addition, with few exceptions, the function and role in disease pathogenesis of the newly defined risk genes is unknown. Thus, the initial harvest of RA loci will catalyze new lines of hypothesis driven research to determine their role in disease pathogenesis. In addition, the rapidly advancing genetic technologies should lead to a more complete definition of the genetic underpinnings or RA in the next few years.