Rheumatoid arthritis: Edited by Lars KlareskogRecent progress in rheumatoid arthritis genetics: one step towards improved patient carePlenge, Robert Ma,bAuthor Information aDivision of Rheumatology, Immunology and Allergy, Brigham and Women's, Hospital, Harvard Medical School, Boston, USA bBroad Institute of MIT and Harvard, Cambridge, Massachusetts, USA Correspondence to Robert Plenge, MD, PhD, Robert Plenge, 77 Avenue Louis Pasteur, Suite 168, Boston, MA 02115, USA Tel: +1 617 525 4451; fax: +1 617 525 4488; e-mail: [email protected] Current Opinion in Rheumatology: May 2009 - Volume 21 - Issue 3 - p 262-271 doi: 10.1097/BOR.0b013e32832a2e2d Buy Metrics Abstract Purpose of review Recent human genetic discoveries have increased our understanding of rheumatoid arthritis (RA) susceptibility. These discoveries are reviewed and placed in the context of potential important clinical applications. Recent findings Genome-wide association studies and related methodologies have expanded the number of validated RA risk loci beyond HLA–DRB1 ‘shared epitope’ alleles to include additional major histocompatibility complex risk alleles and more than 10 regions outside the major histocompatibility complex locus. The newly discovered risk alleles are common in the general population, and most have a modest effect on risk of RA (odds ratio ∼1.15 per copy of each risk allele). Although the actual causal mutation and causal gene for most loci remain to be determined, these studies are beginning to reveal general themes: many risk loci are associated with other autoimmune diseases, many genes fall within discrete biological pathways (e.g., the NF-κB signaling pathway), and human genetics can subset disease into clinically meaningful categories (e.g., presence or absence of autoantibodies). Summary Approximately one-third of the genetic basis of RA can be explained by known risk loci. Future studies need to pinpoint the actual causal mutations, expand the number of risk loci, and translate these discoveries to improve care of patients with RA. © 2009 Lippincott Williams & Wilkins, Inc.