机构：[1]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.首都医科大学附属北京同仁医院首都医科大学附属同仁医院[2]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.[3]State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University, Tianjin, China.[4]Department of Laboratory Medicine and Institute of Precise Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.中山大学附属第一医院[5]Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, California, United States.[6]Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, China.[7]CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.[8]Centre for Innovation & Precision Eye Health, National University of Singapore, Queenstown, Singapore.[9]Henan Academy of Innovations in Medical Science, Henan, China.
To elucidate the genetic basis of primary angle-closure glaucoma (PACG) by identifying pathogenic tissue and critical tissue-specific variants.The correlations among PACG susceptibility, axial length (AL), and anterior chamber depth (ACD) were evaluated using meta-analyses. Propensity score matching was utilized on 2161 participants from the Handan Eye Study to determine the risk factors independent of ACD and AL for PACG. Subsequently, we employed the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to screen 202 PACG genome-wide association study (GWAS) variants for chromatin accessibility and functional roles.The meta-analysis found that PACG susceptibility loci are not associated with ACD or AL. However, abnormal iris phenotypes emerged as significant independent risk factors for primary angle-closure disease (PACD), unrelated to ACD and AL. Substantial enrichment of PACG heritability was observed in the open chromatin regions of the human iris. Within the iris-relevant cellular context, 22 out of the 202 PACG GWAS variants could influence enhancer activity. Two variants in the iris open chromatin regions were implicated in the modulation of PLEKHA7 and C10orf53 expression. The downregulation of these two genes affects cytoskeletal organization.Our findings underscore the importance of the iris in the pathogenesis of PACG and identified iris-specific, enhancer-modulating variants that may influence disease risk. Our approach also provides a generalizable framework for studying ocular diseases from the perspective of enhancer-modulating variants.
基金：
Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes ( JYY2023-6 to NW) and National Natural Science Foundation of China (32070595 to LY, 82371050 to YZ).
第一作者机构：[1]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
共同第一作者：
通讯作者：
通讯机构：[1]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.[2]Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.[6]Kunpeng Institute of Modern Agriculture at Foshan, Chinese Academy of Agricultural Sciences, Foshan, China.[9]Henan Academy of Innovations in Medical Science, Henan, China.
推荐引用方式(GB/T 7714)：
Li Jiaying,Chen Yun,Wang Wenbin,et al.Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics[J].Investigative Ophthalmology & Visual Science.2024,65(14):18.doi:10.1167/iovs.65.14.18.
APA：
Li Jiaying,Chen Yun,Wang Wenbin,Zhang Ye,Su Guangsong...&Wang Ningli.(2024).Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics.Investigative Ophthalmology & Visual Science,65,(14)
MLA：
Li Jiaying,et al."Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics".Investigative Ophthalmology & Visual Science 65..14(2024):18
