Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396422003425 |
| _version_ | 1818163760772153344 |
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| author | Zhengbo Xue Jian Yuan Fukun Chen Yinghao Yao Shilai Xing Xiangyi Yu Kai Li Chenxiao Wang Jinhua Bao Jia Qu Jianzhong Su Hao Chen |
| author_facet | Zhengbo Xue Jian Yuan Fukun Chen Yinghao Yao Shilai Xing Xiangyi Yu Kai Li Chenxiao Wang Jinhua Bao Jia Qu Jianzhong Su Hao Chen |
| author_sort | Zhengbo Xue |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-12-11T16:54:41Z |
| format | Article |
| id | doaj.art-71dafc26205549489e1b5014bffe21c8 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T16:54:41Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-71dafc26205549489e1b5014bffe21c82022-12-22T00:57:59ZengElsevierEBioMedicine2352-39642022-08-0182104161Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK BiobankZhengbo Xue0Jian Yuan1Fukun Chen2Yinghao Yao3Shilai Xing4Xiangyi Yu5Kai Li6Chenxiao Wang7Jinhua Bao8Jia Qu9Jianzhong Su10Hao Chen11Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaWenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325105, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaWenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325105, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaEye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325027, Zhejiang, ChinaEye 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, ChinaEye 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.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).http://www.sciencedirect.com/science/article/pii/S2352396422003425Ocular diseasesCross-disease geneticsGWASGenetic correlationPleiotropyRetinal development |
| spellingShingle | Zhengbo Xue Jian Yuan Fukun Chen Yinghao Yao Shilai Xing Xiangyi Yu Kai Li Chenxiao Wang Jinhua Bao Jia Qu Jianzhong Su Hao Chen Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank EBioMedicine Ocular diseases Cross-disease genetics GWAS Genetic correlation Pleiotropy Retinal development |
| title | Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
| title_full | Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
| title_fullStr | Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
| title_full_unstemmed | Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
| title_short | Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
| title_sort | genome wide association meta analysis of 88 250 individuals highlights pleiotropic mechanisms of five ocular diseases in uk biobank |
| topic | Ocular diseases Cross-disease genetics GWAS Genetic correlation Pleiotropy Retinal development |
| url | http://www.sciencedirect.com/science/article/pii/S2352396422003425 |
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