TY - JOUR 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 DO - 10.3899/jrheum.121034 SP - jrheum.121034 AU - Sebastien Viatte AU - Darren Plant AU - Mark Lunt AU - Bo Fu AU - Edward Flynn AU - Ben J. Parker AU - James Galloway AU - Csilla Solymossy AU - Jane Worthington AU - Deborah P.M. Symmons AU - Josh J. Dixey AU - Adam Young AU - Anne Barton Y1 - 2012/12/15 UR - http://www.jrheum.org/content/early/2012/12/13/jrheum.121034.abstract N2 - 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. ER -