Identification of Novel Risk Loci for Behçet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study.

Abstract

OBJECTIVE:

To explore susceptibility loci associated with uveitis in Behçet's disease (BD).

METHODS:

We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1.

RESULTS:

Three independent HLA alleles (HLA-B51 [3.75 × 10-190 ], HLA-A26 [1.50 × 10-18 ], and HLA-C0704 [3.44 × 10-16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1.

CONCLUSION:

This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.

• Authors: Guannan Su, Zhenyu Zhong, Qingyun Zhou, Liping Du, Zi Ye, Fuzhen Li, Wenjuan Zhuang, Chaokui Wang, Liang Liang, Yan Ji, Qingfeng Cao, Qingfeng Wang, Rui Chang, Handan Tan, Shenglan Yi, Yujing Li, Xiaojie Feng, Weiting Liao, Wanyun Zhang, Jia Shu, Shiyao Tan, Jing Xu, Su Pan, Hongxi Li, Jing Shi, Zhijun Chen, Ying Zhu, Xingsheng Ye, Xiao Tan, Jun Zhang, Zhangluxi Liu, Fanfan Huang, Gangxiang Yuan, Tingting Pang, Yizong Liu, Jiadong Ding, Yingnan Gao, Meifen Zhang, Wei Chi, Xiaoli Liu, Yuqin Wang, Ling Chen, Akira Meguro, Masaki Takeuchi, Nobuhisa Mizuki, Shigeaki Ohno, Xianbo Zuo, Aize Kijlstra, Peizeng Yang
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 74 Issue 4 Pg. 671-681 (04 2022) ISSN: 2326-5205 [Electronic] United States
• PMID: 34652073 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 American College of Rheumatology.

Chemical References

• Carrier Proteins
• FIBP protein, human
• Membrane Proteins

Topics

• Asian People (genetics)
• Behcet Syndrome (genetics)
• Carrier Proteins (genetics)
• China
• Genome-Wide Association Study
• Humans
• Membrane Proteins (genetics)
• Uveitis (genetics)