RT Journal Article
SR Electronic
T1 Investigation of Rheumatoid Arthritis Genetic Susceptibility Markers in the Early Rheumatoid Arthritis Study Further Replicates the <em>TRAF1</em> Association with Radiological Damage
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 144
OP 156
DO 10.3899/jrheum.121034
VO 40
IS 2
A1 SEBASTIEN VIATTE
A1 DARREN PLANT
A1 MARK LUNT
A1 BO FU
A1 EDWARD FLYNN
A1 BEN J. PARKER
A1 JAMES GALLOWAY
A1 CSILLA SOLYMOSSY
A1 JANE WORTHINGTON
A1 DEBORAH P.M. SYMMONS
A1 JOSH J. DIXEY
A1 ADAM YOUNG
A1 ANNE BARTON
YR 2013
UL http://www.jrheum.org/content/40/2/144.abstract
AB Objective. The TRAF1 genetic region conferring susceptibility to rheumatoid arthritis (RA) has been reported to associate with radiological damage. We aimed to test RA genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modeling techniques. Methods. Sixty-seven RA susceptibility variants were genotyped in 474 patients in the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different timepoints. Genetic markers associated with radiological damage in ERAS were tested using the same modeling techniques on previously published data from the Norfolk Arthritis Register (NOAR). Results. The single marker associated longitudinally with Larsen score in ERAS (p = 0.02) and in NOAR (p = 0.04) was rs2900180 at the TRAF1 locus. Analysis of individual timepoints in ERAS showed that rs2900180 displays its effect primarily on the extent of Larsen score early in the disease course. Combined longitudinal analysis of the 2 cohorts suggests further association of several loci with Larsen score (KIF5A, PTPN22, AFF3, TAGAP) and therefore a significant accumulation of RA severity markers among RA susceptibility markers (p = 0.016). Conclusion. The marker rs2900180 is associated with the extent of radiological damage in the ERAS cohort. This represents the second independent study correlating rs2900180 at the TRAF1 locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity.