rs10985070

This functional study integrates epigenomic datasets (ATAC-seq, Hi-C, ChIP-seq, RNA-seq) from fibroblast-like synoviocytes (FLS) to map the functional relevance of 101 fine-mapped rheumatoid arthritis GWAS associations. FLS regulatory elements account for 24% of RA heritability, and the study assigns putative target genes to RA risk loci, identifying TNFAIP3, IFNAR1, CDK6, RBPJ and others as disease-relevant genes. TNF stimulation reveals dynamic chromatin interactions and differential gene expression at RA-associated regulatory regions.

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.