We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
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
- 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.
- Publication
Journal of Crohn's & Colitis, 2024, Vol 18, Issue 1, p47
- ISSN
1873-9946
- Publication type
Article
- DOI
10.1093/ecco-jcc/jjad127