Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study.

IF 3.9 2区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Lipids in Health and Disease Pub Date : 2024-11-04 DOI:10.1186/s12944-024-02337-0
Bin Tong, Chubing Long, Jing Zhang, Xin Zhang, Zhengyang Li, Haodong Qi, Kangtai Su, Deju Zhang, Yixuan Chen, Jitao Ling, Jianping Liu, Yunwei Hu, Peng Yu
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Abstract

Background: Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited.

Methods: Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies.

Results: All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases.

Conclusions: By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

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人类血液代谢组与视神经退行性疾病的关系:一项双向系统泯灭随机研究。
背景:在视神经退行性疾病(OND)患者中观察到代谢紊乱。然而,代谢物与 OND 之间因果关系的证据有限:方法:双样本孟德尔随机法(MR)。从三项全基因组关联研究(GWAS)中选取了 128 种血液代谢物的汇总数据,涉及 147827 名欧洲后裔参与者。青光眼(20906 例病例和 391275 例对照)和老年性黄斑变性(AMD,9721 例病例和 381339 例对照)的全基因组关联研究数据来自 FinnGen 财团。为了评估因果关系,研究人员进行了双向磁共振分析,并进一步应用中介磁共振分析来探讨间接效应,然后进行了全表磁共振分析,以确定疗法可能产生的副作用:所有结果都经过了多重检验校正和严格的敏感性分析。我们发现N-乙酰甘氨酸、丝氨酸、尿苷与青光眼风险升高有关。1-丙烯酰-甘油磷酸酯-乙醇胺、4-乙酰氨基丁酸盐、邻甲基抗坏血酸、饱和脂肪酸、单不饱和脂肪酸、VLDL 胆固醇、血清总胆固醇、X-11,529 与青光眼风险降低有关。色氨酸甜菜碱、4-雄烯-3beta-17beta-二醇二硫酸盐、载脂蛋白B、VLDL胆固醇等4种代谢物与降低老年性黄斑病变风险有关。我们发现眼压、强直性脊柱炎、T2D是青光眼的危险因素,而体重指数、强直性脊柱炎、GCIPL则是AMD的危险因素。6种代谢物与风险因素的关系与它们与青光眼/AMD的关系方向一致。全表型MR表明,选定的代谢物对其他疾病具有保护/不良影响:通过整合基因组学和代谢组学,本研究有助于深入了解复杂的机制,并有助于预防和筛查青光眼和老年性视网膜病变。
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来源期刊
Lipids in Health and Disease
Lipids in Health and Disease 生物-生化与分子生物学
CiteScore
7.70
自引率
2.20%
发文量
122
审稿时长
3-8 weeks
期刊介绍: Lipids in Health and Disease is an open access, peer-reviewed, journal that publishes articles on all aspects of lipids: their biochemistry, pharmacology, toxicology, role in health and disease, and the synthesis of new lipid compounds. Lipids in Health and Disease is aimed at all scientists, health professionals and physicians interested in the area of lipids. Lipids are defined here in their broadest sense, to include: cholesterol, essential fatty acids, saturated fatty acids, phospholipids, inositol lipids, second messenger lipids, enzymes and synthetic machinery that is involved in the metabolism of various lipids in the cells and tissues, and also various aspects of lipid transport, etc. In addition, the journal also publishes research that investigates and defines the role of lipids in various physiological processes, pathology and disease. In particular, the journal aims to bridge the gap between the bench and the clinic by publishing articles that are particularly relevant to human diseases and the role of lipids in the management of various diseases.
期刊最新文献
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