rs3890745

This case-control study of 646 Chinese Han subjects (326 SLE patients, 320 controls) investigated the association between CD40 and CD226 gene polymorphisms and systemic lupus erythematosus (SLE) risk. Carriers of the T allele of rs4810485 in CD40 had significantly elevated SLE risk (OR=1.84, 95% CI 1.40-2.29), as did carriers of the T allele of rs763361 in CD226 (OR=1.89, 95% CI 1.38-2.13). Gene-gene interaction analysis revealed a significant two-locus model (p=0.01) with subjects carrying both risk variants at highest risk (OR=2.14, 95% CI 1.67-3.08).

This extended UK genome-wide association study identified a novel rheumatoid arthritis susceptibility locus at 22q12 (rs1043099, P = 6.9 × 10⁻⁹, OR = 0.84) in 3,034 cases and 5,271 controls, and confirmed 16 previously known RA loci, strengthening evidence for genetic contributors to RA in the UK population.

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 study examined 27 previously identified rheumatoid arthritis (RA) risk alleles in 556 autoantibody-positive African-American RA cases and 791 controls. Twenty-four of 27 SNPs showed consistent odds ratios between African-Americans and Europeans; three SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) showed opposite directions of effect. A genetic risk score analysis indicated that African-American cases were significantly enriched for European RA risk alleles (p=0.00005), suggesting that RA genetic risk factors are largely shared across ancestry groups.

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.