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.