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Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank
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), glau...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297108/ https://www.ncbi.nlm.nih.gov/pubmed/35841873 http://dx.doi.org/10.1016/j.ebiom.2022.104161 |
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author | Xue, Zhengbo Yuan, Jian Chen, Fukun Yao, Yinghao Xing, Shilai Yu, Xiangyi Li, Kai Wang, Chenxiao Bao, Jinhua Qu, Jia Su, Jianzhong Chen, Hao |
author_facet | Xue, Zhengbo Yuan, Jian Chen, Fukun Yao, Yinghao Xing, Shilai Yu, Xiangyi Li, Kai Wang, Chenxiao Bao, Jinhua Qu, Jia Su, Jianzhong Chen, Hao |
author_sort | Xue, Zhengbo |
collection | PubMed |
description | 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). |
format | Online Article Text |
id | pubmed-9297108 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92971082022-07-21 Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank Xue, Zhengbo Yuan, Jian Chen, Fukun Yao, Yinghao Xing, Shilai Yu, Xiangyi Li, Kai Wang, Chenxiao Bao, Jinhua Qu, Jia Su, Jianzhong Chen, Hao eBioMedicine Articles 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). Elsevier 2022-07-15 /pmc/articles/PMC9297108/ /pubmed/35841873 http://dx.doi.org/10.1016/j.ebiom.2022.104161 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Xue, Zhengbo Yuan, Jian Chen, Fukun Yao, Yinghao Xing, Shilai Yu, Xiangyi Li, Kai Wang, Chenxiao Bao, Jinhua Qu, Jia Su, Jianzhong Chen, Hao Genome-wide association meta-analysis of 88,250 individuals highlights pleiotropic mechanisms of five ocular diseases in UK Biobank |
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 | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9297108/ https://www.ncbi.nlm.nih.gov/pubmed/35841873 http://dx.doi.org/10.1016/j.ebiom.2022.104161 |
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