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.
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.