rs6684865

This study applied Bayesian epistasis association mapping (BEAM/BEAM2) methods to genome-wide association studies data from the Welcome Trust Case Control Consortium (WTCCC) to identify high-order SNP interactions in rheumatoid arthritis. The analysis identified 319 high-order epistatic interactions across the genome, with many validated using data from the North American Rheumatoid Arthritis Consortium (NARAC). Key findings include inter-chromosomal interactions primarily on chromosomes 1, 3, 6, and 9, with enriched GO terms implicating synapse, calcium ion binding, and membrane pathways.

This association study examined whether six genetic variants identified in RA susceptibility studies also influence radiographic joint destruction severity. In ACPA-positive RA patients, rs4810485 in CD40 showed significant association with increased radiographic progression rate (1.12x greater annual Sharp score increase per risk allele, P=0.003), which was independently replicated in the NARAC cohort (P=0.021). This represents the first non-HLA-related genetic severity factor for RA progression that has been replicated across independent cohorts.

A case-control association study of 1,316 Korean RA patients and 1,006 controls found that rs7021206 in TRAF1 intron 3 is significantly associated with rheumatoid arthritis susceptibility (OR 1.21, P = 0.0037), while rs3761847, which is associated with RA in Caucasians, showed no association in Koreans due to different linkage disequilibrium patterns. Fine-mapping identified a 66-kb haplotype region spanning TRAF1 containing variants associated with RA across both Asian and Caucasian populations.