크론병-궤양성대장염 질병 간 연관 분석을 통한 유전자좌 발굴

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC), two major subtypes of inflammatory bowel disease, show substantial differences in their clinical course and treatment response. To identify the genetic factors underlying the distinct characteristics of the se two diseases, we performed a genome wide association study (GWAS) between CD (n = 2,359) and UC (n = 2,175) in a Korean population, followed by replication in an independent sample of 772 CD and 619 UC cases. Two novel loci were identified with divergen t effects on CD and UC: rs9842650 in CD200 and rs885026 in NCOR2 . In addition, the 7 established susceptibility loci (MHC , TNFSF15, OTUD3, USP12, IL23R, FCHSD2, and RIPK2) reached genome wide significance. Of the 9 loci, 6 (MHC, TNFSF15, OTUD3, USP12, IL23 R, and CD200) were replicated in the case case GWAS (CC GWAS) of European populations. The proportion of variance explained in CD UC status by polygenic risk score analysis was up to 22.6%. The area under the receiver operating characteristic curve value w as 0.74, suggesting acceptable discrimination between CD and UC. This CD UC GWAS provides new insights into genetic differences between the two diseases with similar symptoms and might be useful in improving their diagnosis and treatment.