rs13140464

This dense genotyping study identified 12 genome-wide significant susceptibility loci for primary sclerosing cholangitis (PSC) outside the HLA complex in 3,789 European PSC cases and 25,079 controls using the Immunochip array. Nine loci were novel, including rs7426056 (CD28; OR=1.30), rs3197999 (MST1; OR=1.33), rs13140464 (IL2/IL21; OR=1.30), rs56258221 (BACH2; OR=1.23), and rs2836883 (PSMG1; OR=1.28). The study found overlapping yet distinct genetic architecture between PSC and inflammatory bowel disease, with PSC being genetically more similar to ulcerative colitis than Crohn's disease.

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.