rs6840978

This study fine-maps the IL2/IL21 genetic association with systemic lupus erythematosus (SLE) in two large independent sample sets: European-derived (4,248 lupus patients, 3,818 controls) and African-American (1,569 patients, 1,893 controls). Using conditional analysis and trans-ethnic mapping, the researchers localized the primary genetic effect to two SNPs in high linkage disequilibrium: rs907715 within IL21 (OR=1.16, 95% CI 1.10-1.22, P=2.17×10⁻⁸) and rs6835457 in the 3'-UTR flanking region of IL21 (OR=1.11, 95% CI 1.05-1.17, P=9.35×10⁻⁵). The findings establish genome-wide significance for the IL2/IL21 locus in lupus genetic susceptibility.

This study confirmed association between rs6822844 in the IL2-IL21 region and multiple autoimmune diseases in non-European populations, with significant associations in Colombian samples for systemic lupus erythematosus (OR 0.50, P=0.008), type 1 diabetes (OR 0.43, P=0.014), rheumatoid arthritis (OR 0.61, P=0.019), and primary Sjögren's syndrome (OR 0.46, P=0.033). Meta-analysis of 23 populations showed highly significant overall association (P=2.61×10⁻²⁵, OR 0.73) and disease-specific associations with inflammatory bowel disease (P=3.48×10⁻¹², OR 0.74), rheumatoid arthritis (P=3.61×10⁻⁶, OR 0.77), type 1 diabetes (P=5.33×10⁻⁵, OR 0.61), and celiac disease (P=5.30×10⁻³, OR 0.72).