Regulatory Variants on the Leukocyte Immunoglobulin-Like Receptor Gene Cluster are Associated with Crohn's Disease and Interact with Regulatory Variants for TAP2
- Authors
- Kim, Kwangwoo; Oh, Shin Ju; Lee, Junho; Kwon, Ayeong; Yu, Chae-Yeon; Kim, Sangsoo; Choi, Chang Hwan; Kang, Sang-Bum; Kim, Tae Oh; Park, Dong Il; Lee, Chang Kyun
- Issue Date
- Jan-2024
- Publisher
- Oxford University Press
- Keywords
- Crohn’s disease; genetic variants; GWAS
- Citation
- Journal of Crohn's & colitis, v.18, no.1, pp 47 - 53
- Pages
- 7
- Journal Title
- Journal of Crohn's & colitis
- Volume
- 18
- Number
- 1
- Start Page
- 47
- End Page
- 53
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/72790
- DOI
- 10.1093/ecco-jcc/jjad127
- ISSN
- 1873-9946
1876-4479
- Abstract
- BACKGROUND AND AIMS: Crohn's disease [CD] has a complex polygenic aetiology with high heritability. There is ongoing effort to identify novel variants associated with susceptibility to CD through a genome-wide association study [GWAS] in large Korean populations. METHODS: Genome-wide variant data from 902 Korean patients with CD and 72 179 controls were used to assess the genetic associations in a meta-analysis with previous Korean GWAS results from 1621 patients with CD and 4419 controls. Epistatic interactions between CD-risk variants of interest were tested using a multivariate logistic regression model with an interaction term. RESULTS: We identified two novel genetic associations with the risk of CD near ZBTB38 and within the leukocyte immunoglobulin-like receptor [LILR] gene cluster [p < 5 × 10-8], with highly consistent effect sizes between the two independent Korean cohorts. CD-risk variants in the LILR locus are known quantitative trait loci [QTL] for multiple LILR genes, of which LILRB2 directly interacts with various ligands including MHC class I molecules. The LILR lead variant exhibited a significant epistatic interaction with CD-associated regulatory variants for TAP2 involved in the antigen presentation of MHC class I molecules [p = 4.11 × 10-4], showing higher CD-risk effects of the TAP2 variant in individuals carrying more risk alleles of the LILR lead variant (odds ratio [OR] = 0.941, p = 0.686 in non-carriers; OR = 1.45, p = 2.51 × 10-4 in single-copy carriers; OR = 2.38, p = 2.76 × 10-6 in two-copy carriers). CONCLUSIONS: This study demonstrated that genetic variants at two novel susceptibility loci and the epistatic interaction between variants in LILR and TAP2 loci confer a risk of CD. © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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