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Meta-Analysis
. 2022 Apr;74(4):671-681.
doi: 10.1002/art.41998. Epub 2022 Feb 14.

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

Guannan Su  1 , Zhenyu Zhong  1 , Qingyun Zhou  1 , Liping Du  2 , Zi Ye  1 , Fuzhen Li  2 , Wenjuan Zhuang  3 , Chaokui Wang  1 , Liang Liang  1 , Yan Ji  1 , Qingfeng Cao  1 , Qingfeng Wang  1 , Rui Chang  1 , Handan Tan  1 , Shenglan Yi  1 , Yujing Li  1 , Xiaojie Feng  1 , Weiting Liao  1 , Wanyun Zhang  1 , Jia Shu  1 , Shiyao Tan  1 , Jing Xu  1 , Su Pan  1 , Hongxi Li  1 , Jing Shi  1 , Zhijun Chen  1 , Ying Zhu  1 , Xingsheng Ye  1 , Xiao Tan  1 , Jun Zhang  1 , Zhangluxi Liu  1 , Fanfan Huang  1 , Gangxiang Yuan  1 , Tingting Pang  2 , Yizong Liu  2 , Jiadong Ding  2 , Yingnan Gao  2 , Meifen Zhang  4 , Wei Chi  5 , Xiaoli Liu  6 , Yuqin Wang  7 , Ling Chen  8 , Akira Meguro  9 , Masaki Takeuchi  9 , Nobuhisa Mizuki  9 , Shigeaki Ohno  10 , Xianbo Zuo  11 , Aize Kijlstra  12 , Peizeng Yang  1
Affiliations
Meta-Analysis

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

Guannan Su et al. Arthritis Rheumatol. 2022 Apr.

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.

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References

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