title: Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.
abstract: Rheumatoid arthritis (RA) is the most common inflammatory arthritis and exhibits genetic overlap with other autoimmune and inflammatory disorders. Although predominant associations with the HLA-DRB1 locus have been known for decades, recent data have revealed additional insight into the likely causative variants within HLA-DRB1 as well as within other HLA loci that contribute to disease risk. In addition, more than 100 common variants in non-HLA loci have been implicated in disease susceptibility. Genetic factors are involved not only in the development of RA, but also with various disease subphenotypes, including production and circulating levels of autoantibodies and joint destruction. The major current challenge is to integrate these new data into a precise understanding of disease pathogenesis, including the critical cell types and molecular networks involved as well as interactions with environmental factors. We predict that delineating the functional effects of genetic variants is likely to drive new diagnostic and therapeutic approaches to the disease.
authors.affiliation: Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.|Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02115.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142; email: soumya@broadinstitute.org.|Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8501, Japan; email: a0001101@kuhp.kyoto-u.ac.jp.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.affiliation: Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.|Partners Center for Personalized Genetic Medicine, Boston, Massachusetts 02115.|Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142; email: soumya@broadinstitute.org.|Institute of Inflammation and Repair, University of Manchester, M15 6SZ Manchester, United Kingdom.|Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden.
authors.forename: Soumya
authors.initials: S
authors.lastname: Raychaudhuri
authors.affiliation: Robert S. Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York 11030; email: peterg@nshs.edu.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006801:Humans
chemical_list: D001323:Autoantibodies; D059811:HLA-DRB1 Chains
keywords: HLA; endophenotype