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Genetic Analysis of Ulcerative Colitis in Japanese Individuals Using Population-specific SNP Array.
- Source :
-
Inflammatory bowel diseases [Inflamm Bowel Dis] 2020 Jul 17; Vol. 26 (8), pp. 1177-1187. - Publication Year :
- 2020
-
Abstract
- Background: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array.<br />Methods: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction.<br />Results: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02).<br />Conclusions: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.<br /> (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Case-Control Studies
Colitis, Ulcerative ethnology
Genetic Loci genetics
Genome-Wide Association Study
Genotype
HLA Antigens genetics
Humans
Japan
Kaplan-Meier Estimate
MicroRNAs blood
Principal Component Analysis
Receptors, Interleukin genetics
Asian People genetics
Colitis, Ulcerative genetics
Genetic Predisposition to Disease genetics
Polymorphism, Single Nucleotide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1536-4844
- Volume :
- 26
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Inflammatory bowel diseases
- Publication Type :
- Academic Journal
- Accession number :
- 32072174
- Full Text :
- https://doi.org/10.1093/ibd/izaa033