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ORIGINAL RESEARCH article

Front. Med.
Sec. Obstetrics and Gynecology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1433612
This article is part of the Research Topic A Lifecourse Perspective on Polycystic Ovary Syndrome (PCOS): Bridging Gaps in Research and Practice View all 8 articles

Genetically Predicted Serum Metabolites Mediate the Association Between Inflammatory Proteins and Polycystic Ovary Syndrome: A Mendelian Randomization Study

Provisionally accepted
Mingjie Jia Mingjie Jia *
  • Guangzhou University of Chinese Medicine, Guangzhou, China

The final, formatted version of the article will be published soon.

    Objective: To investigate the association between polycystic ovary syndrome (PCOS) and inflammatory proteins, and to identify and quantify the role of serum metabolites as potential mediators.Methods: Utilizing summary-level data from a genome-wide association study (GWAS), we conducted a two-sample Mendelian Randomization (MR) analysis, a genetic approach that uses genetic variants as instrumental variables to assess the causal relationships between risk factors and outcomes. This analysis involved genetically predicted PCOS (1,639 cases and 218,970 controls) and inflammatory proteins (14,824 participants of primarily European descent). Additionally, a two-step MR analysis was performed to quantify the proportion of the effect of serum metabolites-mediated inflammatory proteins on PCOS. The Inverse Variance Weighted (IVW) method, a statistical technique used within MR to combine data from multiple genetic variants, was used to estimate the causal effects.Results: The IVW method revealed that the inflammatory proteins IFN-γ (P-value = 0.037, OR = 1.396, 95% CI = 1.020-1.910) and CCL7 (P-value = 0.033, OR = 1.294, 95% CI = 1.021-1.641) were associated with an increased risk of PCOS, while IL-6 (P-value = 0.015, OR = 0.678, 95% CI = 0.495-0.929) and MMP-10 (P-value = 0.025, OR = 0.753, 95% CI = 0.587-0.967) were associated with a decreased risk. No significant evidence suggested an effect of genetically predicted PCOS on inflammatory proteins. The serum metabolite X-11444 was found to mediate 5.44% (95% CI: 10.8%-0.0383%) of the effect of MMP-10 on PCOS.Conclusions: This study not only introduces novel causal associations between inflammatory proteins and PCOS but also highlights the mediating role of serum metabolites in these associations. By applying MR, we were able to minimize confounding and reverse causality, offering robust insights into the biological mechanisms underlying PCOS. These findings advance the understanding of PCOS pathogenesis, particularly in relation to inflammatory pathways and serum metabolite interactions, and suggest potential therapeutic targets that could inform future clinical interventions aimed at mitigating inflammation-related PCOS risks.

    Keywords: Mendelian randomization, Inflammatory proteins, Serum metabolites, Polycystic Ovary Syndrome, pcos

    Received: 16 May 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mingjie Jia, Guangzhou University of Chinese Medicine, Guangzhou, China

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