Genetically predicted blood metabolites mediate the association between circulating immune cells and severe COVID-19: A Mendelian randomization study.

IF 1.3 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Medicine Pub Date : 2024-11-15 DOI:10.1097/MD.0000000000040509

Ning Ai, Yan Zhang, Jing Yang, Yu Zhang, Xuejing Zhao, Huifen Feng

{"title":"Genetically predicted blood metabolites mediate the association between circulating immune cells and severe COVID-19: A Mendelian randomization study.","authors":"Ning Ai, Yan Zhang, Jing Yang, Yu Zhang, Xuejing Zhao, Huifen Feng","doi":"10.1097/MD.0000000000040509","DOIUrl":null,"url":null,"abstract":"<p><p>Investigating the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19 and revealing the role of blood metabolite-mediated circulating immune cells in disease onset and progression. Genetic variation data of 731 circulating immune cells, 1400 blood metabolites, and severe COVID-19 from genome-wide association study open-access database (https://gwas.mrcieu.ac.uk) were used as instrumental variables for bidirectional and two-step Mendelian randomization analysis. The study identified 11 circulating immune cells with unidirectional causality to severe COVID-19. Two-step Mendelian randomization analysis showed 10 blood metabolites were causally associated with severe COVID-19, and blood Myristate and Citrulline to phosphate ratio mediated the association of circulating effector memory double negative % DN and CD8dim natural killer T cell % T cells, respectively, with severe COVID-19 (Myristate mediated effect ratio was 10.20%, P = .011; Citrulline to phosphate ratio mediated effect ratio was -9.21%, P = .017). This study provides genetic evidence assessing the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19, elucidates the role of blood metabolite-mediated circulating immune cells in severe COVID-19 development, and offers new insights into severe COVID-19 etiology and related preventive and targeted therapeutic strategies.</p>","PeriodicalId":18549,"journal":{"name":"Medicine","volume":"103 46","pages":"e40509"},"PeriodicalIF":1.3000,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11575977/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MD.0000000000040509","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

Abstract

Investigating the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19 and revealing the role of blood metabolite-mediated circulating immune cells in disease onset and progression. Genetic variation data of 731 circulating immune cells, 1400 blood metabolites, and severe COVID-19 from genome-wide association study open-access database (https://gwas.mrcieu.ac.uk) were used as instrumental variables for bidirectional and two-step Mendelian randomization analysis. The study identified 11 circulating immune cells with unidirectional causality to severe COVID-19. Two-step Mendelian randomization analysis showed 10 blood metabolites were causally associated with severe COVID-19, and blood Myristate and Citrulline to phosphate ratio mediated the association of circulating effector memory double negative % DN and CD8dim natural killer T cell % T cells, respectively, with severe COVID-19 (Myristate mediated effect ratio was 10.20%, P = .011; Citrulline to phosphate ratio mediated effect ratio was -9.21%, P = .017). This study provides genetic evidence assessing the causal relationship between circulating immune cells, blood metabolites, and severe COVID-19, elucidates the role of blood metabolite-mediated circulating immune cells in severe COVID-19 development, and offers new insights into severe COVID-19 etiology and related preventive and targeted therapeutic strategies.

查看原文本刊更多论文

基因预测的血液代谢物介导了循环免疫细胞与严重 COVID-19 之间的关联：孟德尔随机化研究

研究循环免疫细胞、血液代谢物和重症 COVID-19 之间的因果关系，揭示血液代谢物介导的循环免疫细胞在疾病发生和发展中的作用。研究人员利用全基因组关联研究开放存取数据库（https://gwas.mrcieu.ac.uk）中的731个循环免疫细胞、1400种血液代谢物和重症COVID-19的遗传变异数据作为工具变量，进行了双向和两步孟德尔随机分析。研究发现，11 种循环免疫细胞与严重 COVID-19 存在单向因果关系。两步孟德尔随机分析显示，10种血液代谢物与重度COVID-19有因果关系，血液中肉豆蔻酸盐和瓜氨酸与磷酸比分别介导了循环效应记忆双阴性% DN和CD8dim自然杀伤T细胞% T细胞与重度COVID-19的关联（肉豆蔻酸盐介导的效应比为10.20%，P = .011；瓜氨酸与磷酸比介导的效应比为-9.21%，P = .017）。这项研究提供了遗传学证据，评估了循环免疫细胞、血液代谢物和重症 COVID-19 之间的因果关系，阐明了血液代谢物介导的循环免疫细胞在重症 COVID-19 发生中的作用，并为重症 COVID-19 的病因及相关预防和靶向治疗策略提供了新的见解。

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

Medicine 医学-医学：内科

CiteScore

2.80

自引率

0.00%

发文量

4342

审稿时长

>12 weeks

期刊介绍： Medicine is now a fully open access journal, providing authors with a distinctive new service offering continuous publication of original research across a broad spectrum of medical scientific disciplines and sub-specialties. As an open access title, Medicine will continue to provide authors with an established, trusted platform for the publication of their work. To ensure the ongoing quality of Medicine’s content, the peer-review process will only accept content that is scientifically, technically and ethically sound, and in compliance with standard reporting guidelines.