Causal Relationships Between Circulating Inflammatory Proteins and Obstructive Sleep Apnea: A Bidirectional Mendelian Randomization Study

Abstract

Purpose

Clinical studies have demonstrated the intricate association between the onset and progression of obstructive sleep apnea (OSA) and the activation of the inflammatory cascade reaction. This study delves into investigating the causal links between 91 circulating inflammatory proteins (CIPs) and OSA through the application of Mendelian randomization (MR) techniques.

Methods

Utilizing genetic data on OSA sourced from the Finnish Biobank (FinnGen) Genome-wide Association Studies (GWAS) of the European population, alongside summary-level GWAS data of CIPs from 14,824 European participants, we conducted a bidirectional MR study.

Results

This study suggests that several factors may be associated with the risk of OSA. IL-17C (odds ratio (OR) = 1.090, p = 0.0311), CCL25 (OR = 1.079, p = 0.0493), FGF-5 (OR = 1.090, p = 0.0003), CD5 (OR = 1.055, p = 0.0477), and TNFSF14 (OR = 1.092, p = 0.0008) may positively correlate with OSA risk. Conversely, IL-20RA (OR = 0.877, p = 0.0107), CCL19 (OR = 0.933, p = 0.0237), MIP-1 alpha (OR = 0.906, p = 0.0042), Flt3L (OR = 0.941, p = 0.0019), CST5 (OR = 0.957, p = 0.0320), OPG (OR = 0.850, p = 0.0001), and TRAIL (OR = 0.956, p = 0.0063) may reduce the risk of OSA. Additionally, elevated levels of IL-10RA (OR = 1.153, p = 0.0478) were observed as a consequence of OSA. Conversely, OSA may potentially lead to decreased levels of CCL28 (OR = 0.875, p = 0.0317), DNER (OR = 0.874, p = 0.0324), FGF-21 (OR = 0.846, p = 0.0344), and CSF-1 (OR = 0.842, p = 0.0396).

Conclusion

Through this bidirectional MR study, we have identified 12 upstream regulatory proteins and 5 downstream effect proteins that are linked to OSA. These findings hold promise in providing potential therapeutic targets for the inflammatory mechanisms underlying OSA.

Keywords:

• Mendelian randomization
• bidirectional
• obstructive sleep apnea
• circulating inflammatory proteins

Data Sharing Statement

The original contributions proposed in this study are located in the main text/supplementary materials. The GWAS data used has been appropriately cited. Further inquiries can be directed to the corresponding author.

Ethics Approval

The present study was strictly conducted in accordance with the Declaration of Helsinki and International Ethical Guidelines for Health-related Research Involving Humans. This study obtained approval from the Medical Ethics Committee of Tianjin Chest Hospital, with review opinion number 2024LW-007.

Acknowledgments

The authors wish to express gratitude to the researchers and participants involved in the original GWAS and FinnGen biobank for their efforts in collecting and managing extensive data resources, as well as those who actively participated in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was funded by grants from National Clinical Key Specialty Construction Project, Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-049A).