Beyond association: Mediation roles of lipidomics and cytokine in PCOS uncovered by cross-disciplinary genomics

IF 2.6 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Prostaglandins & other lipid mediators Pub Date : 2026-07-01 Epub Date: 2026-06-23 DOI:10.1016/j.prostaglandins.2026.107090

Tingyu Lang, Yongxiu Yang

{"title":"Beyond association: Mediation roles of lipidomics and cytokine in PCOS uncovered by cross-disciplinary genomics","authors":"Tingyu Lang, Yongxiu Yang","doi":"10.1016/j.prostaglandins.2026.107090","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><div>Polycystic ovary syndrome (PCOS) is a metabolic disorder that significantly impacts female fertility. Lipids and inflammation are key factors in the pathogenesis and progression of PCOS. This study aims to elucidate the complex causal relationships involving 179 lipids, 91 inflammatory markers, and PCOS using robust Mendelian Randomization (MR) methods based on Genome-Wide Association Studies (GWAS). Additionally, we seek to quantify the mediating effects of inflammation markers on lipid in PCOS.</div></div><div><h3>Methods and results</h3><div>After rigorous screening of eligible SNPs, IVW was employed, supplemented by Simple mode, Weighted median, Weighted mode, and Bayesian Weighted Mendelian Randomization analyses. Sensitivity analyses were performed to ensure result accuracy. Mediation analysis was conducted to identify inflammation factors mediating the lipid-PCOS pathway. We identified 11 lipids causally associated with PCOS, including sterol esters, phosphatidylcholine, sphingomyelin, and triacylglycerol. MR Analysis linked these lipids to 58 inflammatory factors, of which only two were associated with PCOS, with β-NGF increasing the risk of PCOS by 6.50% and uPA reducing it by 4.60%. Mediator analysis showed the effect of uPA-mediated phosphatidylcholine (18:2_20:4) on PCOS.</div></div><div><h3>Conclusion</h3><div>This study is the first to use MR to explore causal links between lipids, inflammatory factors, and PCOS. We identified uPA as a key mediator and uncovered 11 lipids significantly associated with PCOS, highlighting the phosphatidylcholine (18:2_20:4)-uPA-PCOS pathway. Our findings suggest targeting lipid metabolism and using phosphatidylcholine (18:2_20:4) and uPA as biomarkers and tools for evaluating therapeutic efficacy in PCOS.</div></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":"185 ","pages":"Article 107090"},"PeriodicalIF":2.6000,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins & other lipid mediators","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1098882326000353","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/6/23 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and aims

Polycystic ovary syndrome (PCOS) is a metabolic disorder that significantly impacts female fertility. Lipids and inflammation are key factors in the pathogenesis and progression of PCOS. This study aims to elucidate the complex causal relationships involving 179 lipids, 91 inflammatory markers, and PCOS using robust Mendelian Randomization (MR) methods based on Genome-Wide Association Studies (GWAS). Additionally, we seek to quantify the mediating effects of inflammation markers on lipid in PCOS.

Methods and results

After rigorous screening of eligible SNPs, IVW was employed, supplemented by Simple mode, Weighted median, Weighted mode, and Bayesian Weighted Mendelian Randomization analyses. Sensitivity analyses were performed to ensure result accuracy. Mediation analysis was conducted to identify inflammation factors mediating the lipid-PCOS pathway. We identified 11 lipids causally associated with PCOS, including sterol esters, phosphatidylcholine, sphingomyelin, and triacylglycerol. MR Analysis linked these lipids to 58 inflammatory factors, of which only two were associated with PCOS, with β-NGF increasing the risk of PCOS by 6.50% and uPA reducing it by 4.60%. Mediator analysis showed the effect of uPA-mediated phosphatidylcholine (18:2_20:4) on PCOS.

Conclusion

This study is the first to use MR to explore causal links between lipids, inflammatory factors, and PCOS. We identified uPA as a key mediator and uncovered 11 lipids significantly associated with PCOS, highlighting the phosphatidylcholine (18:2_20:4)-uPA-PCOS pathway. Our findings suggest targeting lipid metabolism and using phosphatidylcholine (18:2_20:4) and uPA as biomarkers and tools for evaluating therapeutic efficacy in PCOS.

查看原文本刊更多论文

超越关联：跨学科基因组学揭示的脂质组学和细胞因子在多囊卵巢综合征中的中介作用。

背景与目的：多囊卵巢综合征（PCOS）是一种严重影响女性生育能力的代谢性疾病。脂质和炎症是多囊卵巢综合征发病和进展的关键因素。本研究旨在利用基于全基因组关联研究（GWAS）的孟德尔随机化（MR）方法，阐明涉及179种脂质、91种炎症标志物和多囊卵巢综合征的复杂因果关系。此外，我们试图量化炎症标志物对PCOS中脂质的介导作用。方法和结果：在严格筛选符合条件的snp后，采用IVW，并辅以简单模式、加权中位数、加权模式和贝叶斯加权孟德尔随机化分析。进行敏感性分析以确保结果的准确性。进行中介分析以确定介导脂质- pcos通路的炎症因子。我们确定了11种与多囊卵巢综合征有因果关系的脂质，包括甾酯、磷脂酰胆碱、鞘磷脂和三酰甘油。MR分析将这些脂质与58种炎症因子联系起来，其中只有两种与多囊卵巢综合征有关，β-NGF使多囊卵巢综合征的风险增加6.50%，uPA使其降低4.60%。中介分析显示，upa介导的磷脂酰胆碱（18:2_20:4）对PCOS有影响。结论：本研究首次使用磁共振技术探索脂质、炎症因子和多囊卵巢综合征之间的因果关系。我们确定了uPA是PCOS的关键介质，并发现了11种与PCOS显著相关的脂质，突出了磷脂酰胆碱(18:2_20:4)-uPA-PCOS途径。我们的研究结果建议以脂质代谢为靶点，利用磷脂酰胆碱（18:2_20 . 4）和uPA作为评价PCOS治疗效果的生物标志物和工具。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Prostaglandins & other lipid mediators 生物-生化与分子生物学

CiteScore

5.80

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： Prostaglandins & Other Lipid Mediators is the original and foremost journal dealing with prostaglandins and related lipid mediator substances. It includes basic and clinical studies related to the pharmacology, physiology, pathology and biochemistry of lipid mediators. Prostaglandins & Other Lipid Mediators invites reports of original research, mini-reviews, reviews, and methods articles in the basic and clinical aspects of all areas of lipid mediator research: cell biology, developmental biology, genetics, molecular biology, chemistry, biochemistry, physiology, pharmacology, endocrinology, biology, the medical sciences, and epidemiology. Prostaglandins & Other Lipid Mediators also accepts proposals for special issue topics. The Editors will make every effort to advise authors of the decision on the submitted manuscript within 3-4 weeks of receipt.