rs42041

This multi-cohort genetic association study of 1,283 RA patients found that the PTPRC/CD45 gene variant rs10919563 (G allele) is associated with favorable response to anti-TNF therapy (OR 0.55, P=0.0001). Of 31 established RA risk alleles tested, only PTPRC reached genome-wide significance for therapy response, with stronger associations in autoantibody-positive patients (OR 0.55, 95% CI 0.39-0.76) compared to seronegative patients.

This association study of 664 German Wegener's granulomatosis (WG) patients and 952 controls evaluated 22 SNPs across 13 candidate genes identified from RA and SLE studies. The strongest finding was a protective four-SNP IRF5 haplotype (rs2004640_G/rs60344245_del/rs2070197_T/rs10954213_G) with reduced WG risk (p=0.0000897, OR 0.73, 95% CI 0.62-0.85). SNPs in TNFAIP3 and CDK6 also showed nominally significant associations, suggesting WG shares some genetic risk factors with other autoimmune diseases.

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.