TRAF1–C5 as a Risk Locus for Rheumatoid Arthritis — A Genomewide Study
Open accessAbstract
Background Rheumatoid arthritis has a complex mode of inheritance. Although HLA-DRB1 and PTPN22 are well-established susceptibility loci, other genes that confer a modest level of risk have been identified recently. We carried out a genomewide association analysis to identify additional genetic loci associated with an increased risk of rheumatoid arthritis. Methods We genotyped 317,503 single-nucleotide polymorphisms (SNPs) in a combined case-control study of 1522 case subjects with rheumatoid arthritis and 1850 matched control subjects. The patients were seropositive for autoantibodies against cyclic citrullinated peptide (CCP). We obtained samples from two data sets, the North American Rheumatoid Arthritis Consortium (NARAC) and the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Results from NARAC and EIRA for 297,086 SNPs that passed quality-control filters were combined with the use of Cochran-Mantel-Haenszel stratified analysis. SNPs showing a significant association with disease (P Results We observed associations between disease and variants in the major-histocompatibility-complex locus, in PTPN22, and in a SNP (rs3761847) on chromosome 9 for all samples tested, the latter with an odds ratio of 1.32 (95% confidence interval, 1.23 to 1.42; P=4x10(-14)). The SNP is in linkage disequilibrium with two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5). C…
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This is the first study to suggest the involvement of TBX3 in B cell proliferation and development of CIA, and adds mechanistic links to three independent GWAS that linked TBX3 to RA.
“To our knowledge, this is the first study to suggest the involvement of TBX3 in B cell proliferation and development of CIA, and adds mechanistic links to three independent genome-wide association studies (GWAS) that linked TBX3 to RA [65–67].”
From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [65]
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References 50 · Cited by 823
- Authors
- Plenge, R. M., Seielstad, M., Padyukov, L., Lee, A. T., Remmers, E. F., Ding, B., Liew, A., Khalili, H., Chandrasekaran, A., Davies, L. R. L., Li, W., Tan, A. K. S., Bonnard, C., Ong, R. T. H., Thalamuthu, A., Pettersson, S., Liu, C., Tian, C., Chen, W. V., Carulli, J. P., Beckman, E. M., Altshuler, D., Alfredsson, L., Criswell, L. A., Amos, C. I., Seldin, M. F., Kastner, D. L., Klareskog, L., & Gregersen, P. K.
- Affiliations
- Broad Institute (US)
- ORCID
- Plenge, Robert M.
- Seielstad, Mark
- Padyukov, Leonid
- Remmers, Elaine F.
- Ding, Bo
- Chandrasekaran, Alamelu
- Davies, Leela R.L.
- Li, Wentian
- Bonnard, Carine
- Ong, Rick T.H.
- Thalamuthu, Anbupalam
- Pettersson, Sven
- Liu, Chunyu
- Carulli, John P.
- Altshuler, David
- Alfredsson, Lars
- Criswell, Lindsey A.
- Kastner, Daniel L.
- Klareskog, Lars
- Gregersen, Peter K.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2007-09-20
- Volume
- 357
- Issue
- 12
- Pages
- 1199-1209
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2636867
- OpenAlex
- W2162276444
- Cited by
- 823
- References
- 50
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 18 · 2023: 11 · 2022: 16 · 2021: 8 · 2020: 15 · 2019: 19 · 2018: 20 · 2017: 28 · 2016: 30 · 2015: 35 · 2014: 39 · 2013: 58 · 2012: 58
- FWCI
- 87.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01ar022263-007, 5r01ai065841-05, 5m01rr000079-42)
- National Institute of Allergy and Infectious Diseases (R01-AI-065841, K08 AI55314-3, K08AI055314)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR044422, N01-AR-22263, K24-AR-02175, N01 AR022263, R01 AR44422, K24AR002175, R01AR050267)
- National Center for Research Resources (5M01-RR00079, M01-RR000079, M01RR018535)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- rheumatoid arthritis, chromosome 9, genetic susceptibility, anti-citrullinated protein antibodies, HLA-DRB1, PTPN22, single nucleotide polymorphisms, major histocompatibility complex, chronic inflammation, genetic association
- MeSH terms
- Arthritis, Rheumatoid, Autoantibodies, Chromosome Mapping, Chromosomes, Human, Pair 9, Complement C5, Genotype, HLA-DR Antigens, Humans, Peptides, Cyclic, Risk Factors, Linkage Disequilibrium, Logistic Models, Case-Control Studies, Protein Tyrosine Phosphatases, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, TNF Receptor-Associated Factor 1, Protein Tyrosine Phosphatase, Non-Receptor Type 22, HLA-DRB1 Chains
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