{"title":"从欧洲人群的循环蛋白到血浆代谢物探索年龄相关性黄斑变性的治疗靶点。","authors":"Chengming Chen, Yanyan Lan, Weiming Yan, Xiaohong Zhang, Tian Li, Jing Han","doi":"10.1167/tvst.14.5.8","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD).</p><p><strong>Methods: </strong>We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. This investigation utilized data from protein quantitative trait loci (pQTL) studies in deCODE and the UK Biobank. Additionally, plasma metabolite-related genome-wide association studies (GWAS) data and AMD-related GWAS data were incorporated.</p><p><strong>Results: </strong>Our findings confirmed a potential causal relationship between cytoplasmic tryptophanyl-tRNA synthetase 1 (WARS1) and a higher risk of AMD. The observed causal impact of WARS1 on the two subtypes of AMD (dry and wet) align consistently with the aforementioned outcomes. Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD.</p><p><strong>Conclusions: </strong>The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. Nevertheless, further research is essential to validate and strengthen these conclusions.</p><p><strong>Translational relevance: </strong>This study establishes the causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD.</p>","PeriodicalId":23322,"journal":{"name":"Translational Vision Science & Technology","volume":"14 5","pages":"8"},"PeriodicalIF":2.6000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063708/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.\",\"authors\":\"Chengming Chen, Yanyan Lan, Weiming Yan, Xiaohong Zhang, Tian Li, Jing Han\",\"doi\":\"10.1167/tvst.14.5.8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD).</p><p><strong>Methods: </strong>We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. 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Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD.</p><p><strong>Conclusions: </strong>The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. 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引用次数: 0
摘要
目的：探讨循环蛋白、血浆代谢物与年龄相关性黄斑变性（AMD）之间的因果关系。方法：采用孟德尔随机化（MR）分析和共定位分析来确定蛋白质组与AMD之间的因果关系。本研究利用了deCODE和UK Biobank的蛋白质数量性状位点（pQTL）研究数据。此外，还纳入了血浆代谢物相关的全基因组关联研究（GWAS）数据和amd相关的GWAS数据。结果：我们的研究结果证实了细胞质色氨酸- trna合成酶1 （war1）与AMD高风险之间的潜在因果关系。观察到的war1对两种AMD亚型（干性和湿性）的因果影响与上述结果一致。三种血浆代谢物- n -乙酰基犬尿氨酸、n -乙酰基酪氨酸和己酸(6:0)-被确定为WARS1对AMD因果效应的介质，亚组分析显示n -乙酰基酪氨酸是与WARS1和干性AMD相关的特异性阴性代谢物，而X-16580是与WARS1和湿性AMD相关的特异性阳性代谢物。结论：本研究的结果提示了特定循环蛋白在AMD中的潜在因果作用，并通过整合多种遗传分析确定了血浆代谢物在WARS1和AMD之间的介导作用。然而，进一步的研究是必要的，以验证和加强这些结论。翻译相关性：本研究确立了特定循环蛋白在AMD中的因果作用，并确定了血浆代谢物在war1与AMD之间的中介作用。
Exploring Therapeutic Targets for Age-Related Macular Degeneration From Circulating Proteins to Plasma Metabolites in the European Population.
Purpose: To explore the causal associations among circulating proteins, plasma metabolites, and age-related macular degeneration (AMD).
Methods: We employed Mendelian randomization (MR) analysis and colocalization analysis to discern the causal relationship between proteomes and AMD. This investigation utilized data from protein quantitative trait loci (pQTL) studies in deCODE and the UK Biobank. Additionally, plasma metabolite-related genome-wide association studies (GWAS) data and AMD-related GWAS data were incorporated.
Results: Our findings confirmed a potential causal relationship between cytoplasmic tryptophanyl-tRNA synthetase 1 (WARS1) and a higher risk of AMD. The observed causal impact of WARS1 on the two subtypes of AMD (dry and wet) align consistently with the aforementioned outcomes. Three plasma metabolites-N-acetyl-kynurenine, N-acetyltyrosine, and caproate (6:0)-were identified as mediators of the causal effect of WARS1 on AMD, and subgroup analysis revealed that N-acetyltyrosine is a specific negative metabolite associated with WARS1 and dry AMD, whereas X-16580 is a specific positive metabolite linked to WARS1 and wet AMD.
Conclusions: The outcomes of this study suggest a potential causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD by integrating multiple genetic analyses. Nevertheless, further research is essential to validate and strengthen these conclusions.
Translational relevance: This study establishes the causal role of specific circulating proteins in AMD and identified the mediating role of plasma metabolites between WARS1 and AMD.
期刊介绍：
Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO.
The journal covers a broad spectrum of work, including but not limited to:
Applications of stem cell technology for regenerative medicine,
Development of new animal models of human diseases,
Tissue bioengineering,
Chemical engineering to improve virus-based gene delivery,
Nanotechnology for drug delivery,
Design and synthesis of artificial extracellular matrices,
Development of a true microsurgical operating environment,
Refining data analysis algorithms to improve in vivo imaging technology,
Results of Phase 1 clinical trials,
Reverse translational ("bedside to bench") research.
TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.
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