Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank
Zhengbo Xue,
Jian Yuan,
Fukun Chen,
Yinghao Yao,
Shilai Xing,
Xiangyi Yu,
Kai Li,
Chenxiao Wang,
Jinhua Bao,
Jia Qu,
Jianzhong Su,
Hao Chen
Affiliations
Zhengbo Xue
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Jian Yuan
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Fukun Chen
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Yinghao Yao
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325105, Zhejiang, China
Shilai Xing
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Xiangyi Yu
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Kai Li
Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325105, Zhejiang, China
Chenxiao Wang
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Jinhua Bao
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
Jia Qu
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, China
Jianzhong Su
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325105, Zhejiang, China; Corresponding authors at: Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, 270 West Xueyuan Road, Wenzhou 325027, Zhejiang, China.
Hao Chen
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; Corresponding authors at: Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, 270 West Xueyuan Road, Wenzhou 325027, Zhejiang, China.
Summary: Background: Ocular diseases may exhibit common clinical symptoms and epidemiological comorbidity. However, the extent of pleiotropic mechanisms across ocular diseases remains unclear. We aim to examine shared genetic etiology in age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, retinal detachment (RD), and myopia. Methods: We analyzed genome-wide association analyses for the five ocular diseases in 43,877 cases and 44,373 controls of European ancestry from UK Biobank, estimated their genetic relationships (LDSC, GNOVA, and Genomic SEM), and identified pleiotropic loci (ASSET and METASOFT). Findings: The genetic correlation of common SNPs revealed a meaningful genetic structure within these diseases, identifying genetic correlations between AMD, DR, and glaucoma. Cross-trait meta-analysis identified 23 pleiotropic loci associated with at least two ocular diseases and 14 loci unique to individual disorders (non-pleiotropic). We found that the genes associated with these shared genetic loci are involved in neuron differentiation (P = 8.80 × 10−6) and eye development systems (P = 3.86 × 10−5), and single cell RNA sequencing data reveals their heightened gene expression from multipotent progenitors to other differentiated retinal cells during retina developmental process. Interpretation: These results highlighted the potential common genetic architectures among these ocular diseases and can deepen the understanding of the molecular mechanisms underlying the related diseases. Funding: The National Natural Science Foundation of China (61871294), Zhejiang Provincial Natural Science Foundation of China (LR19C060001), and the Scientific Research Foundation for Talents of Wenzhou Medical University (QTJ18023).
