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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cytokines and Soluble Mediators in Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1416870

Effect of Inflammatory Cytokines and Plasma Metabolome on OSA: A Bidirectional Two-Sample Mendelian Randomization Study and Mediation Analysis

Provisionally accepted
Xin Sun Xin Sun 1Congying Wang Congying Wang 1*Yuheng He Yuheng He 2*Kun Chen Kun Chen 1*Yingzhang Miao Yingzhang Miao 2*
  • 1 Hebei North University, Zhangjiakou, China
  • 2 Hebei General Hospital, Shijiazhuang, Hebei Province, China

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

    Background: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. Methods: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships.The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. Conclusions: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

    Keywords: obstructive sleep apnea, 91 plasma proteins, plasma-based metabolites, bidirectional two-sample mendelian randomization, Mediation analysis

    Received: 13 Apr 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Sun, Wang, He, Chen and Miao. 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:
    Congying Wang, Hebei North University, Zhangjiakou, China
    Yuheng He, Hebei General Hospital, Shijiazhuang, 050051, Hebei Province, China
    Kun Chen, Hebei North University, Zhangjiakou, China
    Yingzhang Miao, Hebei General Hospital, Shijiazhuang, 050051, Hebei Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.