Letter abstract
Nature Genetics 41, 820 - 823 (2009)
Published online: 7 June 2009 | doi:10.1038/ng.395
REL, encoding a member of the NF-
B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis
Peter K Gregersen1,14, Chistopher I Amos2,14, Annette T Lee1, Yue Lu2, Elaine F Remmers3, Daniel L Kastner3, Michael F Seldin4, Lindsey A Criswell5, Robert M Plenge6, V Michael Holers7, Ted R Mikuls8, Tuulikki Sokka9, Larry W Moreland10, S Louis Bridges Jr11, Gang Xie12, Ann B Begovich13 & Katherine A Siminovitch12
Abstract
We conducted a genome-wide association study of rheumatoid arthritis in 2,418 cases and 4,504 controls from North America and identified an association at the REL locus, encoding c-Rel, on chromosome 2p13 (rs13031237, P = 6.01 
10-10). Replication in independent case-control datasets comprising 2,604 cases and 2,882 controls confirmed this association, yielding an allelic OR = 1.25 (P = 3.08 10-14) for marker rs13031237 and an allelic OR = 1.21 (P = 2.60 10-11) for marker rs13017599 in the combined dataset. The combined dataset also provides definitive support for associations at both CTLA4 (rs231735; OR = 0.85; P = 6.25 10-9) and BLK (rs2736340; OR = 1.19; P = 5.69 10-9). c-Rel is an NF-
B family member with distinct functional properties in hematopoietic cells, and its association with rheumatoid arthritis suggests disease pathways that involve other recently identified rheumatoid arthritis susceptibility genes including CD40, TRAF1, TNFAIP3 and PRKCQ1, 2.
- The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, New York, USA.
- University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
- Genetics and Genomics Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
- Rowe Program in Genetics, University of California at Davis, Davis, California, USA.
- Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, California, USA.
- Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- University of Colorado Denver School of Medicine, Denver, Colorado, USA.
- University of Nebraska Medical Center, Omaha, Nebraska, USA.
- Jyväskylä Central Hospital, Jyväskylä, Finland.
- University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
- University of Alabama at Birmingham, Birmingham, Alabama, USA.
- Mount Sinai Hospital and University Health Network, Toronto, Ontario, Canada.
- Celera, Alameda, California, USA.
- These authors contributed equally to this work.
Correspondence to: Peter K Gregersen1,14 e-mail: peterg@nshs.edu
Correspondence to: Katherine A Siminovitch12 e-mail: ksimin@mshri.on.ca
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