Identification of Ten Additional Susceptibility Loci for Ulcerative Colitis Through Immunochip Analysis in Koreans

Abstract

Background Recent genetic association studies identified more than 160 susceptibility loci for inflammatory bowel disease in Caucasian populations, but studies in Asian populations are limited. We have previously reported 3 loci associated with Korean ulcerative colitis (UC).

Methods Using the Immunochip custom single nucleotide polymorphisms (SNP) array designed for dense genotyping of 186 known disease loci from 12 immune-mediated diseases, we analyzed 705 patients with UC and 1178 controls for 536,821 SNPs (89,057 genotyped and 447,764 imputed) in the discovery stage followed by replication in additional 980 affected individuals and 2694 controls in a Korean population.

Results We confirmed the associations of 10 known UC risk loci in Koreans: rs76418789 in IL23R (combined P = 1.25 × 10⁻⁸), rs4728142 in IRF5 (combined P = 3.17 × 10⁻⁸), rs1830610 near JAK2 (combined P = 2.28 × 10⁻⁹), rs1555791 near TNFRSF14 (combined P = 1.62 × 10⁻⁶), rs880790 between IL10-IL19 (combined P = 3.73 × 10⁻⁶), rs10185424 between IL1R2-IL1R1 (combined P = 1.54 × 10⁻⁴), rs6478108 in TNFSF15 (combined P = 9.28 × 10⁻⁵), rs861857 between UBE2L3-YDJC (combined P = 3.05 × 10⁻⁵), rs1801274 in FCGR2A (discovery P = 1.54 × 10⁻⁴), and rs17085007 between GPR12-USP12 (discovery P = 3.64 × 10⁻⁴). The percentage of phenotype variance explained by the 13 risk loci (including 3 previously reported loci) was 5.61% in Koreans (on the liability scale, population prevalence = 0.0308%).

Conclusions Our study increased the number of UC susceptibility loci in Koreans to 13 and highlighted the extensive sharing of genetic risk across populations of UC.