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.
| Original language | English |
|---|---|
| Pages (from-to) | 2274-2279 |
| Number of pages | 5 |
| Journal | Human Molecular Genetics |
| Volume | 17 |
| Issue number | 15 |
| Early online date | 22 Apr 2008 |
| DOIs | |
| Publication status | Published - Aug 2008 |
Keywords
- TYROSINE-PHOSPHATASE
- RISK
- POPULATION
- PTPN22
- VARIANT
- 6Q23
- RA
Cite this
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, A.; Thomson, W.; Ke, X.; Eyre, S.; Hinks, A.; Bowes, J.; Gibbons, L.; Plant, D.; Wilson, A. G.; Marinou, I.; Morgan, A.; Emery, P.; Steer, S.; Hocking, Lynne; Reid, David M; Wordsworth, P.; Harrison, P.; Worthington, J.; Wellcome Trust Case Control Consortium.
In: Human Molecular Genetics, Vol. 17, No. 15, 08.2008, p. 2274-2279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility.
AU - Barton, A.
AU - Thomson, W.
AU - Ke, X.
AU - Eyre, S.
AU - Hinks, A.
AU - Bowes, J.
AU - Gibbons, L.
AU - Plant, D.
AU - Wilson, A. G.
AU - Marinou, I.
AU - Morgan, A.
AU - Emery, P.
AU - Steer, S.
AU - Hocking, Lynne
AU - Reid, David M
AU - Wordsworth, P.
AU - Harrison, P.
AU - Worthington, J.
AU - Wellcome Trust Case Control Consortium
PY - 2008/8
Y1 - 2008/8
N2 - 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.
AB - 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.
KW - TYROSINE-PHOSPHATASE
KW - RISK
KW - POPULATION
KW - PTPN22
KW - VARIANT
KW - 6Q23
KW - RA
U2 - 10.1093/hmg/ddn128
DO - 10.1093/hmg/ddn128
M3 - Article
VL - 17
SP - 2274
EP - 2279
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 15
ER -