Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23.

Orozco, G., Hinks, A., Eyre, S., Ke, X. Y., Gibbons, L. J., Bowes, J., Flynn, E., Martin, P., Wellcome Trust Case Control Consortium, Brown, Matthew A., Linda Bradbury and et al (2009) Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23.. Human Molecular Genetics, 18 14: 2693-2699. doi:10.1093/hmg/ddp193


Author Orozco, G.
Hinks, A.
Eyre, S.
Ke, X. Y.
Gibbons, L. J.
Bowes, J.
Flynn, E.
Martin, P.
Wellcome Trust Case Control Consortium
Brown, Matthew A.
Linda Bradbury
et al
Title Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23.
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2009-07-15
Year available 2009
Sub-type Article (original research)
DOI 10.1093/hmg/ddp193
Volume 18
Issue 14
Start page 2693
End page 2699
Total pages 7
Editor Davies, K.
Place of publication United Kingdom
Publisher Oxford University Press
Collection year 2010
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
970106 Expanding Knowledge in the Biological Sciences
920116 Skeletal System and Disorders (incl. Arthritis)
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
110322 Rheumatology and Arthritis
Abstract he most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for.
Keyword SYSTEMIC-LUPUS-ERYTHEMATOSUS
NF-KAPPA-B
RHEUMATOID-ARTHRITIS
ASSOCIATION
CLASSIFICATION
RESPONSES
TNFAIP3
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
UQ Diamantina Institute Publications
 
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Created: Wed, 14 Apr 2010, 14:24:29 EST by Kylie Hengst on behalf of UQ Diamantina Institute