rs934734

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 study of 1,115 UK rheumatoid arthritis patients receiving anti-TNF biologic therapy found that rs10919563 in the PTPRC gene was associated with improved treatment response (regression coefficient 0.19, 95% CI 0.09-0.37, P=0.04 for continuous DAS28 outcome; OR 0.62, 95% CI 0.40-0.95, P=0.03 for good EULAR response). Meta-analysis with a previous study strengthened evidence (P=5.13×10⁻⁵). Secondary analysis identified rs11594656 in IL2RA associated with good EULAR response (OR 1.47, P=0.02).

A GWAS of juvenile idiopathic arthritis in 814 cases and 3058 controls identified novel susceptibility loci at 3q13 and 10q21. The most significant associations were at rs4688011 (C3orf1/CD80, OR=1.37, P=1.88×10⁻⁶), rs6479891 (JMJD1C, OR=1.59, P=6.1×10⁻⁸), rs12411988 (JMJD1C, OR=1.57, P=1.16×10⁻⁷), and rs10995450 (NRBF2-EGR2, OR=1.31, P=6.74×10⁻⁵). Replication and meta-analysis in 1744 cases and 7010 controls confirmed associations for the four loci. eQTL analysis showed cis associations with C3orf1 and JMJD1C expression.

This meta-analysis of 7 genome-wide association studies identified three novel multiple sclerosis susceptibility loci: rs170934 near EOMES (3p24.1, OR=1.17, P=1.6×10⁻⁸), rs2150702 in MLANA (9p24.1, OR=1.16, P=3.3×10⁻⁸), and rs6718520 near THADA (2p21, OR=1.17, P=3.4×10⁻⁸). The analysis encompassed 5,545 cases and 12,153 controls and identified 10 additional loci with suggestive evidence of association (P<1×10⁻⁶), including IL12B, TAGAP, PLEK, and ZMIZ1, which are shared with other inflammatory diseases.

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.