Causal relationship between immune cells, metabolites and polycystic ovary syndrome identified by Mendelian randomization and mediation analyses.

IF 3.2 4区 医学 Q3 CELL BIOLOGY
Lan Li, Yang Mo, Ximing Yu, Bing He, Yue Dai, Longlong Fan, Sijie Yang, Huiping Liu
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引用次数: 0

Abstract

Immune cells and blood metabolites play essential roles in the development of polycystic ovary syndrome (PCOS); however, it remains unclear whether blood metabolites mediate the causal relationship between immune cells and PCOS. This study aimed to delineate the causal relationships among immune cells, PCOS and potential blood metabolites through Mendelian randomization (MR). A two-sample MR analysis was conducted using inverse variance weighting as the primary method to determine the causation between immune cells and PCOS risk. This was supplemented by a two-step MR analysis to assess the mediating role of blood metabolites between immune cells and PCOS. In addition, a series of sensitivity analysis methods were employed to test the robustness of the results. We also performed a reverse MR to evaluate the possibility of reverse causal relationships. Our findings identified 22 immune cell phenotypes causally linked to PCOS, with 12 acting as risk factors and 10 as protective factors for PCOS. Furthermore, 45 blood metabolites or ratios were causally related to PCOS. Mediation analysis revealed that X-25519 levels mediated 9.2% of the causal relationship between the absolute count of CD28-CD25++ CD8br and PCOS. In addition, N-acetylglucosamine/n-acetylgalactosamine levels and adenosine 5'-monophosphate levels mediated 6.7% and -11.1%, respectively, in the causation between naive DN(CD4- CD8-) %T cell and PCOS. The aspartate-to-citrate ratio mediated 8.6% of the causal relationship between CD20- CD38- %B cells and PCOS. Finally, reverse MR studies did not identify any reverse causation between the 22 immune cell phenotypes and PCOS. This study elucidates the causal links between immune cells and PCOS, highlighting the potential roles of four blood metabolites in mediating the interaction between immune cells and PCOS, thus providing new targets for research and therapeutic interventions.

免疫细胞、代谢物与多囊卵巢综合征的因果关系:孟德尔随机化和中介分析
免疫细胞和血液代谢产物在多囊卵巢综合征(PCOS)的发展中起重要作用然而,血液代谢物是否介导免疫细胞与多囊卵巢综合征之间的因果关系尚不清楚。本研究旨在通过孟德尔随机化(MR)来描述免疫细胞、多囊卵巢综合征和潜在血液代谢物之间的因果关系。采用反方差加权作为主要方法进行双样本MR分析,以确定免疫细胞与PCOS风险之间的因果关系。通过两步磁共振分析来评估血液代谢物在免疫细胞和多囊卵巢综合征之间的中介作用。此外,采用一系列敏感性分析方法检验结果的稳健性。我们还进行了反向MR来评估反向因果关系的可能性。我们的研究结果确定了22种与PCOS有因果关系的免疫细胞表型,其中12种作为PCOS的危险因素,10种作为PCOS的保护因素。此外,45种血液代谢物或比率与PCOS有因果关系。中介分析显示,X-25519水平介导了CD28-CD25++ CD8br绝对计数与PCOS之间9.2%的因果关系。此外,n-乙酰氨基葡萄糖/n-乙酰半乳糖胺水平和5′-单磷酸腺苷水平在幼稚DN(CD4- CD8-) %T细胞与PCOS之间的因果关系中分别介导6.7%和-11.1%。CD20- CD38- %B细胞与PCOS之间8.6%的因果关系由天冬氨酸与柠檬酸盐的比例介导。最后,反向MR研究未发现22种免疫细胞表型与PCOS之间存在任何反向因果关系。本研究阐明了免疫细胞与PCOS之间的因果关系,强调了四种血液代谢物在介导免疫细胞与PCOS相互作用中的潜在作用,从而为研究和治疗干预提供了新的靶点。
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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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