Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility

Barton, Anne, Wellcome Trust Case Control Consortium, Brown, Matthew A., Bradbury, Linda A. and et al. (2008) Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility. Human Molecular Genetics, 17 15: 2274-2279. doi:10.1093/hmg/ddn128


Author Barton, Anne
Wellcome Trust Case Control Consortium
Brown, Matthew A.
Bradbury, Linda A.
et al.
Title Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
1460-2083
Publication date 2008-08-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddn128
Volume 17
Issue 15
Start page 2274
End page 2279
Total pages 6
Place of publication Oxford, U.K.
Publisher Oxford University Press
Language eng
Subject 0604 Genetics
Formatted abstract
Rheumatoid arthritis (RA) is an archetypal, common, complex autoimmune disease with both genetic and environmental contributions to disease aetiology. Two novel RA susceptibility loci have been reported from recent genome-wide and candidate gene association studies. We, therefore, investigated the evidence for association of the STAT4 and TRAF1/C5 loci with RA using imputed data from the Wellcome Trust Case Control Consortium (WTCCC). No evidence for association of variants mapping to the TRAF1/C5 gene was detected in the 1860 RA cases and 2930 control samples tested in that study. Variants mapping to the STAT4 gene did show evidence for association (rs7574865, P = 0.04). Given the association of the TRAF1/C5 locus in two previous large case-control series from populations of European descent and the evidence for association of the STAT4 locus in the WTCCC study, single nucleotide polymorphisms mapping to these loci were tested for association with RA in an independent UK series comprising DNA from >3000 cases with disease and >3000 controls and a combined analysis including the WTCCC data was undertaken. We confirm association of the STAT4 and the TRAF1/C5 loci with RA bringing to 5 the number of confirmed susceptibility loci. The effect sizes are less than those reported previously but are likely to be a more accurate reflection of the true effect size given the larger size of the cohort investigated in the current study.
© 2008 The Author(s).
Keyword Antibodies
Arthritis, Rheumatoid
Chromosome mapping
Human genome
Cyclic peptides
Polymorphism, Single Nucleotide
STAT4 transcription factor
TNF receptor-associated factor 1
Q-Index Code C1
Q-Index Status Provisional Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 102 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 113 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 01 Apr 2010, 11:20:31 EST by June Temby on behalf of UQ Diamantina Institute