Fine mapping and replication of genetic risk loci in primary sclerosing cholangitis

Abstract Background and aims. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the bile ducts eventually leading to biliary cirrhosis. Recent genetic studies in PSC have identified associations at 2q13, 2q35, 3p21, 4q27, 13q31 and suggestive association at 10p15. The aim of this study was to further characterize and refine the genetic architecture of PSC. Methods. We analyzed previously reported associated SNPs at four of these non-HLA loci and 59 SNPs tagging the IL-2/IL-21 (4q27) and IL2RA (10p15) loci in 992 UK PSC cases and 5162 healthy UK controls. Results. The most associated SNPs identified were rs3197999 (3p21 (MST1), p = 1.9 × 10-6, ORA vs G = 1.28, 95% CI (1.16–1.42)); rs4147359 (10p15 (IL2RA), p = 2.6 × 10-4, ORA vs G = 1.20, 95% CI (1.09–1.33)) and rs12511287 (4q27 (IL-2/IL-21), p = 3.0 × 10-4, ORA vs T = 1.21, 95% CI (1.09–1.35)). In addition, we performed a meta-analysis for selected SNPs using published sum...