单位：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.重庆医科大学附属第一医院[2]The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.[3]Department of Ophthalmology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.[4]Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.[5]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.[6]Ophthalmologic Center of the Second Hospital, Jilin University, Ziqiang Street 218, Changchun, China.[7]The Eye Hospital of Wenzhou Medical University, Wenzhou, China.[8]The Eye and ENT Hospital of Fudan University, Shanghai, China.[9]Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan.[10]Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.[11]China-Japan Friendship Hospital, Beijing, China, and No. 1 Hospital, Anhui Medical University, Anhui, China[12]University Eye Clinic Maastricht, Maastricht, The Netherlands.
Objective. To explore susceptibility loci associated with uveitis in Behcet'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 x 10(-190)], HLA-A26 [1.50 x 10(-18)], and HLA-C0704 [3.44 x 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.
基金：
Natural Science Foundation Major International (Regional) Joint Research Project [81720108009]; National Natural Science Foundation Key Program [81930023]; Chongqing Outstanding Scientists Project (2019); Chongqing Key Laboratory of Ophthalmology (CSTC) [2008CA5003]; Chongqing Science & Technology Platform and Base Construction Program [cstc2014pt-sy10002]; Chongqing Chief Medical Scientist Project (2018); National Natural Science Foundation Project [81800816]; National Key Research and Development Plan for Precision Medicine Research [2017YFC0910002]
第一作者单位：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.
共同第一作者：
通讯作者：
通讯机构：[1]The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China.[11]China-Japan Friendship Hospital, Beijing, China, and No. 1 Hospital, Anhui Medical University, Anhui, China[*1]Peizeng No. 1 Friendship Road, Yuanjiagang, Yuzhong District Chongqing, China 400016[*2]Yinghuadongjie No. 2, Chaoyang District, Beijing, China, 100029
推荐引用方式(GB/T 7714)：
Su Guannan,Zhong Zhenyu,Zhou Qingyun,et al.Identification of Novel Risk Loci for Behcet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study[J].ARTHRITIS & RHEUMATOLOGY.2022,74(4):671-681.doi:10.1002/art.41998.
APA：
Su Guannan,Zhong Zhenyu,Zhou Qingyun,Du Liping,Ye Zi...&Yang Peizeng.(2022).Identification of Novel Risk Loci for Behcet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study.ARTHRITIS & RHEUMATOLOGY,74,(4)
MLA：
Su Guannan,et al."Identification of Novel Risk Loci for Behcet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study".ARTHRITIS & RHEUMATOLOGY 74..4(2022):671-681
医学