rs6897932

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 cohort study of 2,324 subjects with inflammatory polyarthritis tested 17 rheumatoid arthritis (RA) susceptibility SNPs for association with all-cause and cardiovascular disease (CVD) mortality. Carriage of the CCL21 risk allele rs2812378 was associated with increased CVD mortality (HR 1.33, 95% CI 1.01-1.75) and all-cause mortality (HR 1.40, 95% CI 1.04-1.87), with the strongest effects observed in anti-CCP antibody-positive patients with both the CCL21 risk alleles and shared epitope (SE) alleles (all-cause HR 3.20, 95% CI 1.52-6.72; CVD HR 3.73, 95% CI 1.30-10.72). SNPs at the TRAF1/C5 locus were not significantly associated with mortality in this study.

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.

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 pathway-based association study identified genetic variations in the IL7RA/IL7 signaling pathway that increase multiple sclerosis susceptibility. Two novel genes replicated in an independent dataset: IL7 (rs2587156, p=8.29×10−6, OR=1.35) and SOCS1 (rs441349, p=3.48×10−7, OR=1.25). Additional candidate genes with suggestive evidence include PRKCE (p=3.47×10−4), BCL2 (p=4.32×10−4), and TYK2. The study analyzed 2,961 MS cases and controls in discovery, with 4,831 samples in replication, examining 7,865 SNPs across 73 genes in this biologically-relevant immune pathway.

A retrospective association study of 95 Brazilian multiple sclerosis (MS) patients examined HLA alleles and five SNPs (rs4774, rs3087456, rs6897932, rs731236, rs1033182) for associations with MRI lesion load. The HLA-DQA1*04:01 allele was significantly associated with higher lesion load on T2/FLAIR MRI sequences (p=0.02), with 71% of carriers showing above-median lesion load compared to 41% of non-carriers. No significant associations were found between the five SNPs and any MRI features studied.

This case-control association study replicates the CAPSL-IL7R locus association with type 1 diabetes in Spanish (301 cases, 646 controls) and Dutch (429 cases, 720 controls) cohorts. The CAPSL rs1445898 TT genotype confers protection (pooled Mantel-Haenszel OR 0.71, p=0.005), with stronger protective effect in early-onset patients (OR 0.26, p=0.001). IL7R rs6897932 TT genotype also shows protection in early-onset cases (OR 0.18, p=0.02).

A meta-analysis of 4,107 type 2 diabetes cases and 5,187 controls from three GWA studies found no evidence that common variants altering circulating inflammatory protein levels (IL-18, IL-6R, CRP, IL1RN, PAI1, MIF) or variants predisposing to autoimmune diseases (type 1 diabetes, rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, SLE) are associated with type 2 diabetes risk. For example, rs2250417 in IL18 showed OR=1.00 (95% CI 0.99-1.03) versus the expected OR of ~1.15 if inflammation were causal, suggesting inflammatory markers are likely secondary rather than causative in type 2 diabetes.