rs10181656

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.

A case-control study of 675 Chinese female SLE patients and 679 controls found that STAT4 rs7582694 is strongly associated with systemic lupus erythematosus susceptibility (OR=0.68, 95% CI: 0.58-0.79, P=1.13×10⁻⁶). However, no significant associations were found between rs7582694 and any of the 11 SLE clinical subphenotypes examined, including nephritis, arthritis, autoantibodies, and neuropsychiatric disorders.

This case-control association study of juvenile idiopathic arthritis (JIA) in 809 JIA cases and 3,521 controls identified susceptibility loci shared with other autoimmune diseases. Three novel loci were identified: PTPN2 (strongest signals rs7234029, p=7.19×10⁻¹¹, OR=1.59; rs1893217, p=3.48×10⁻⁸, OR=1.52; rs2542151, p=3.05×10⁻⁷, OR=1.45), COG6 (rs7993214, p=3.98×10⁻³, OR=0.79), and ANGPT1 (rs1010824, p=4.93×10⁻³, OR=0.77). Four previously reported JIA loci were confirmed: PTPN22, STAT4, C12orf30, and IL2-IL21. Odds ratios ranged from 1.20 to 1.65 in meta-analysis of initial and independent replication cohorts (n=1,015 cases and 1,568 controls).

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.

A large case-control study of 4,374 SLE cases and 4,860 controls from multiple racial/ethnic groups identified strong genetic associations between multiple SNPs in the STAT4 gene and systemic lupus erythematosus (SLE), with the strongest association at rs10168266 (p=1.38×10⁻¹⁵ in Europeans, combined p=7.02×10⁻²⁵). Multiple significant haplotypes spanning the STAT4 gene were found across European, Asian-Korean, Hispanic, and African American populations, with conditional analyses suggesting rs10168266 explains the primary haplotypic association. In contrast, STAT1 showed only weak suggestive associations.

Two independent candidate gene association studies identified SNPs in TBX21 and STAT4 as significant risk factors for systemic sclerosis in North American whites. TBX21 rs11650354 (TT genotype) conferred 3.37-fold increased risk in recessive mode (P=1.4×10⁻¹⁵, combined N=902 cases/4,745 controls), while STAT4 rs11889341 A allele increased risk 1.29-fold in dominant mode (P=2.4×10⁻⁵, combined N=1,039 cases/3,322 controls). Gene-gene interaction analysis revealed synergistic effects on SSc susceptibility with altered Th1/Th2 cytokine profiles.

This multi-population case-control replication study examined the STAT4 polymorphism rs7574865 in 2,072 rheumatoid arthritis (RA) patients and 2,474 controls across Spain, Sweden, and The Netherlands. The T allele of rs7574865 showed significant association with RA risk with combined effect size OR 1.25 (95% CI 1.13-1.37, P = 9.79 × 10^-6). Meta-analysis across all published populations confirmed the association with OR 1.25 (95% CI 1.19-1.33, P = 1 × 10^-5).