Journal
NATURE GENETICS
Volume 42, Issue 6, Pages 508-U56Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.582
Keywords
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Categories
Funding
- US National Institutes of Health (NIH) [R01-AR057108, R01-AR056768, U54 RR020278]
- Fox Trot Fund
- William Randolph Hearst Fund of Harvard University
- Burroughs Wellcome Fund
- NIH [1K08AR055688-01A1, NO1-AR-2-2263, RO1 AR44422, R01 AI065841, 5-M01-RR-00079, P01 CA87969, CA49449, CA67262, CA50385, AR049880-06, AR47782]
- American College of Rheumatology Bridge Grant
- EMBO-UNESCO L'Oreal Fellowship
- National Center for Research Resources [U54 RR020278]
- Crescendo
- Swedish Medical Research council
- Swedish Council for Working Life and Social Research
- Swedish Rheumatism Foundation
- Vinnova
- AFA
- National Institute of Arthritis
- Musculoskeletal and Skin Diseases of the US National Institutes of Health
- Canadian Institutes for Health Research [MOP79321, IIN-84042]
- Ontario Research Fund [RE01061]
- Canada Research Chair
- Arthritis Research campaign arc [17552]
- Manchester Biomedical Research Centre
- Manchester Academy of Health Sciences
- Netherlands Organization for Scientific Research (VICI) [918.66.620]
- Existing Epidemiological Data (STAMPEED) genomics research program [R01HL087676]
- National Center for Research Resources
- Biogen-Idec
- King Gustaf V's 80-year foundation
- US National Institutes of Health and National Heart, Lung, and Blood Institute
- Stockholm County Council
- NATIONAL CANCER INSTITUTE [R01CA067262, R01CA050385, R01CA049449, P01CA087969, U01CA067262, U01CA049449] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000079, U54RR020278] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL087676] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI065841] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [K08AR055688, N01AR022263, R01AR057108, R01AR056768, R01AR044422, ZIAAR041139, R01AR049880, P60AR047782, R01AR059648] Funding Source: NIH RePORTER
- National Institute for Health Research [NF-SI-0508-10299] Funding Source: researchfish
- Versus Arthritis [19356, 18475] Funding Source: researchfish
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To identify new genetic risk factors for rheumatoid arthritis, we conducted a genome-wide association study meta-analysis of 5,539 autoantibody-positive individuals with rheumatoid arthritis (cases) and 20,169 controls of European descent, followed by replication in an independent set of 6,768 rheumatoid arthritis cases and 8,806 controls. Of 34 SNPs selected for replication, 7 new rheumatoid arthritis risk alleles were identified at genome-wide significance (P < 5 x 10(-8)) in an analysis of all 41,282 samples. The associated SNPs are near genes of known immune function, including IL6ST, SPRED2, RBPJ, CCR6, IRF5 and PXK. We also refined associations at two established rheumatoid arthritis risk loci (IL2RA and CCL21) and confirmed the association at AFF3. These new associations bring the total number of confirmed rheumatoid arthritis risk loci to 31 among individuals of European ancestry. An additional 11 SNPs replicated at P < 0.05, many of which are validated autoimmune risk alleles, suggesting that most represent genuine rheumatoid arthritis risk alleles.
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