rs2233434

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.

This case-control study identified PLD4 as a novel susceptibility gene for systemic sclerosis (SSc) in a Japanese population, with rs2841277 showing significant association (P=0.00017, OR=1.25). The study also confirmed associations between SSc and rs6932056 in TNFAIP3 (P=0.0000095, OR=1.50) and rs2280381 in IRF8 (P=0.0030, OR=1.26). rs2841280 in PLD4 exon 2 was found in strong linkage disequilibrium with rs2841277 and introduces an amino acid change (E27Q).