A comprehensive map of disease networks and molecular drug discoveries for glaucoma.
A comprehensive map of disease networks and molecular drug discoveries for glaucoma.
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青光眼疾病网络和分子药物发现的综合图谱。
DOI：
10.1038/s41598-020-66350-w
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发表时间：
2020
影响因子：
4.6
通讯作者：
Huang Lulin
中科院分区：
文献类型：
--
作者：
Wang Haixin;Deng Yanhui;Wan Ling;Huang Lulin
青光眼是全世界不可逆转失明的主要原因。青光眼的分子病因复杂且不清楚。目前，可用于治疗青光眼的药物很少。本研究的目的是基于青光眼基因，包括遗传因素和差异表达（DE）基因，对青光眼候选药物/化学物质进行系统分析。总共，来自遗传数据库的 401 个基因和来自 DE 基因分析的 1656 个基因被纳入进一步分析。青光眼相关遗传因素方面，54条通路显着富集（FDR < 0.05），DE基因显着富集96条通路（FDR < 0.05）。在 PheWAS 数据库中搜索与青光眼相关基因相关的疾病返回了 1,289 种疾病，在搜索与 DE 青光眼相关基因相关的疾病时返回了 1,356 种疾病。心血管疾病、神经退行性疾病、癌症、眼科疾病与青光眼基因高度相关。对 DGIdb、KEGG 和 CLUE 数据库的搜索发现了一组针对青光眼基因的药物/化学品。随后对四川省人民医院 136,128 名患者的候选药物使用情况和青光眼发病情况的电子病历 (EMR) 进行分析，发现了 9 种候选药物。在这些药物中，接受尼卡地平治疗的个体青光眼发病率最低。结合药物数据库中的信息，突出显示了 40 种最有可能用于青光眼治疗的候选药物。基于这些发现，我们得出结论：青光眼的分子机制很复杂，可能是全身性疾病的反映。可以开发一套针对青光眼基因的即用型候选药物用于青光眼临床药物治疗。我们的结果提供了对青光眼基因、与其他系统性疾病的相互作用以及候选药物/化学物质的系统解释。
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.