TY - JOUR
T1 - TRAF1-C5 as a risk locus for rheumatoid arthritis - A genomewide study
AU - Plenge, Robert M.
AU - Seielstad, Mark
AU - Padyukov, Leonid
AU - Lee, Annette T.
AU - Remmers, Elaine F.
AU - Ding, Bo
AU - Liew, Anthony
AU - Khalili, Houman
AU - Chandrasekaran, Alamelu
AU - Davies, Leela R.L.
AU - Li, Wentian
AU - Tan, Adrian K.S.
AU - Bonnard, Carine
AU - Ong, Rick T.H.
AU - Thalamuthu, Anbupalam
AU - Pettersson, Sven
AU - Liu, Chunyu
AU - Tian, Chao
AU - Chen, Wei V.
AU - Carulli, John P.
AU - Beckman, Evan M.
AU - Altshuler, David
AU - Alfredsson, Lars
AU - Criswell, Lindsey A.
AU - Amos, Christopher I.
AU - Seldin, Michael F.
AU - Kastner, Daniel L.
AU - Klareskog, Lars
AU - Gregersen, Peter K.
PY - 2007/9/20
Y1 - 2007/9/20
N2 - 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<1×10-8) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). 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 = 4×10-14). 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). Conclusions: A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis.
AB - 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<1×10-8) were genotyped in an independent set of case subjects with anti-CCP-positive rheumatoid arthritis (485 from NARAC and 512 from EIRA) and in control subjects (1282 from NARAC and 495 from EIRA). 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 = 4×10-14). 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). Conclusions: A common genetic variant at the TRAF1-C5 locus on chromosome 9 is associated with an increased risk of anti-CCP-positive rheumatoid arthritis.
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U2 - 10.1056/NEJMoa073491
DO - 10.1056/NEJMoa073491
M3 - Article
C2 - 17804836
AN - SCOPUS:34548849168
SN - 0028-4793
VL - 357
SP - 1199
EP - 1209
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 12
ER -