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A comprehensive map of disease networks and molecular drug discoveries for glaucoma.

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机构: [1]The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Center of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China [3]Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China. [4]Department of Ophthalmology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
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Glaucoma is the leading cause of irreversible blindness worldwide. The molecular etiology of glaucoma is complex and unclear. At present, there are few drugs available for glaucoma treatment. The aim of the present study was to perform a systematic analysis of glaucoma candidate drugs/chemicals based on glaucoma genes, including genetic factors and differentially expressed (DE) genes. In total, 401 genes from the genetic databases and 1656 genes from the DE gene analysis were included in further analyses. In terms of glaucoma-related genetic factors, 54 pathways were significantly enriched (FDR < 0.05), and 96 pathways for DE genes were significantly enriched (FDR < 0.05). A search of the PheWAS database for diseases associated with glaucoma-related genes returned 1,289 diseases, and a search for diseases associated with DE glaucoma-related genes returned 1,356 diseases. Cardiovascular diseases, neurodegenerative diseases, cancer, and ophthalmic diseases were highly related to glaucoma genes. A search of the DGIdb, KEGG, and CLUE databases revealed a set of drugs/chemicals targeting glaucoma genes. A subsequent analysis of the electronic medical records (EMRs) of 136,128 patients treated in Sichuan Provincial People's Hospital for candidate drug usage and the onset of glaucoma revealed nine candidate drugs. Among these drugs, individuals treated with nicardipine had the lowest incidence of glaucoma. Taken together with the information from the drug databases, the 40 most likely candidate drugs for glaucoma treatment were highlighted. Based on these findings, we concluded that the molecular mechanism of glaucoma is complex and may be a reflection of systemic diseases. A set of ready-to-use candidate drugs targeting glaucoma genes may be developed for glaucoma clinical drug treatments. Our results provide a systematic interpretation of glaucoma genes, interactions with other systemic diseases, and candidate drugs/chemicals.

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出版当年[2020]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
最新[2023]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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出版当年[2020]版:
Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Center of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China [3]Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
通讯作者:
通讯机构: [1]The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Center of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences, Chengdu, Sichuan, China [3]Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
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