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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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  11. Effect Of Inflammatory Cytokines And Plasma Metabolome On Osa: A Bidirectional Two- Sample Mendelian Randomization Study And Mediation Analysis

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis

Xin Sun1,2, Congying Wang2, Yuheng He1

  • 1Hebei General Hospital, Shijiazhuang, Hebei, China.

Frontiers in Immunology
|October 1, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

This study identifies elevated Eotaxin as a risk factor for obstructive sleep apnea (OSA). It also reveals that reduced levels of two metabolites, X-11849 and X-24978, are linked to increased OSA risk, aiding diagnosis.

Area of Science:

  • Genetics
  • Metabolomics
  • Sleep Medicine

Background:

  • Obstructive sleep apnea (OSA) is a prevalent sleep disorder.
  • Inflammatory factors and plasma metabolites are implicated in OSA progression.
  • The causal links between these factors and OSA are not fully understood, hindering early diagnosis and treatment.

Purpose of the Study:

  • To investigate the causal relationships between plasma proteins, metabolites, and obstructive sleep apnea (OSA).
  • To identify potential biomarkers for early diagnosis and improved treatment strategies for OSA.
  • To explore the genetic underpinnings of OSA development and prognosis.

Main Methods:

  • Utilized Mendelian randomization (MR) analysis on large-scale genetic data from the FinnGen database (43,901 OSA cases, 366,484 controls).
Keywords:
91 plasma proteinsbidirectional two-sample Mendelian randomizationmediation analysisobstructive sleep apnea

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  • Employed 91 plasma proteins from 11 cohorts as instrumental variables (IVs).
  • Conducted a genome-wide association study (GWAS) for replication and employed various MR methods (IVW, MR Egger, weighted median, etc.) with sensitivity analyses.

    • Main Results:

    • Elevated Eotaxin levels were significantly correlated with an increased risk of OSA (OR=1.050, p < 0.05).
    • Reduced levels of metabolites X-11849 and X-24978 were associated with a higher risk of OSA (7.1% and 8.4% decreases, respectively).
    • Sensitivity analyses confirmed the reliability of these findings.

    Conclusions:

    • Identified Eotaxin as a novel potential biomarker for obstructive sleep apnea (OSA).
    • Discovered two previously unrecognized metabolites (X-11849 and X-24978) strongly associated with OSA risk.
    • These findings highlight the role of inflammatory factors and metabolites in the genetic basis of OSA, offering potential for improved diagnostics and therapeutics.
    plasma-based metabolites