| 摘要: |
| 目的:基于两样本孟德尔随机化方法来探索1400种血液代谢物与血栓闭塞性脉管炎（Thromboangiitis obliterans,TAO）之间的因果关系。
方法：我们使用开放GWAS项目中可公开访问的全基因组关联数据，包括8299名欧洲人群的血液代谢物数据和114例TAO病例及381977名对照的数据，以1400种血液代谢物为暴露，TAO为结局，主要采用逆方差加权法进行因果分析，MR-Egger回归、加权中位数法和加权模式法作为补充分析方法。利用MR-Egger回归截距、Cochrane’s Q检验、MR-PRESSO和留一法进行敏感性分析，以增强结果的稳健性。运用Metabo Analyst平台对代谢物进行代谢通路分析。
结果:本研究发现，41种已知血液代谢物与TAO存在因果关联，其中N2,N2-二甲基鸟苷等20种血液代谢物是TAO的危险因素，而十四碳二烯酸酯（14:2）等21种血液代谢物是TAO的保护因素。敏感性分析结果佐证了因果关联的稳健性和可靠性。代谢通路分析结果显示，叶酸介导的一碳单位代谢，甘氨酸、丝氨酸和苏氨酸代谢和核黄素代谢等3条代谢通路与TAO相关。
结论:本研究从1400种血液代谢物中挖掘出41种与TAO发病风险存在因果关联的血液代谢物，分析发现3条代谢通路可能参与了TAO的发病，为TAO的诊治提供了潜在的干预靶点，并有助于TAO的筛查和机制研究。 |
| 关键词: 1400种血液代谢物 孟德尔随机化 血栓闭塞性脉管炎 全基因组关联研究 |
| DOI： |
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| 基金项目:江苏省卫生健康委科研项目 |
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| Causal association study of 1400 blood metabolites with thromboangiitis obliterans based on Mendelian randomization analysis |
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Geyanfeng, liubin, aixiaoming, taozheng
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Affiliated hospital of Jiangsu University
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| Abstract: |
| Objective: To explore the causal association between 1400 blood metabolites and Thromboangiitis obliterans (TAO) based on a two-sample Mendelian randomization approach.
Methods: We utilized publicly available genome-wide association data from open GWAS projects, including blood metabolite data from 8,299 European individuals and data from 114 TAO cases and 381,977 controls. We used 1,400 blood metabolites as exposures and TAO as the outcome, primarily employing inverse variance weighting for causal analysis, MR-Egger regression, weighted median method, and weighted pattern method were used as supplementary analysis methods. Sensitivity analysis was performed using MR-Egger regression intercept, Cochrane’s Q test, MR-PRESSO, and leave-one-out method to enhance the robustness of the results. Perform metabolic pathway analysis of metabolites using the Metabo Analyst platform.
Results:In this study, 41 known blood metabolites were found to be causally associated with TAO, of which 20 blood metabolites,including N2,N2-dimethylguanosine,were risk factors for TAO, while 21 blood metabolites, including tetradecadienoate (14:2), were protective factors for TAO. The results of sensitivity analyses corroborated the robustness and reliability of the causal associations.Metabolic pathway analysis revealed that three pathways—one carbon pool by folate, glycine, serine and threonine metabolism, and riboflavin metabolism—are associated with TAO.
Conclusion:This study identified 41 blood metabolites with causal associations to TAO risk among 1,400 blood metabolites. Analysis revealed three metabolic pathways potentially involved in TAO pathogenesis, providing potential intervention targets for TAO diagnosis and treatment while aiding TAO screening and mechanism research. |
| Key words: 1400 blood metabolites Mendelian randomization thromboangiitis obliterans genome-wide association study |