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, L., Reid, D. M., Wordsworth, P., Harrison, P., Worthington, J., Fraser, Christine, Green, Elaine, Grozeva, Detelina, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Jones, Ian Richard ORCID: https://orcid.org/0000-0001-5821-5889, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Nikolov, Ivan, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 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) , pp. 2274-2279. 10.1093/hmg/ddn128

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Additional Information:	Christine Fraser, Elaine Green, Detelina Grozeva, Marian Hamshere, Peter Holmans, Ian Jones, George Kirov, Valentina Moskvina, Ivan Nikolov, Michael O'Donovan, Michael Owen, Nick Craddock are collaborators on this article.
Publisher:	Oxford University Press
ISSN:	0964-6906
Last Modified:	17 Nov 2022 12:38
URI:	https://orca.cardiff.ac.uk/id/eprint/82220

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