Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis

Abstract

Background

Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases.

Methods

In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells.

Results

Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases.

Conclusion

This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.

Keywords:

• sleep apnea syndrome
• osteoarthritis
• Mendelian randomization
• bioinformatics

Ethics Approval

The Ethics Committee of the affiliated hospital of Southwest Medical University strictly adheres to the Declaration of Helsinki and the International Ethical Guidelines for Health-related Research Involving Humans, performing independent ethical review responsibilities. This study uses legally obtained publicly available data, meeting the conditions for exemption from review as stated in the Ethical Review Methods for Life Sciences and Medical Research Involving Humans.

Author Contributions

All authors made significant contributions to the conception, study design, execution, data acquisition, analysis, and interpretation. All authors have written the article and made substantial revisions and critical reviews of it. All authors have agreed on the journal to which the article will be submitted. All authors have reviewed and agreed on all versions of the article at each stage, and have given approval for the final version to be published. All authors agree to take responsibility and be accountable for the contents of the article.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was supported by the Key R & D Project for Social Development in Sichuan (2020YFS0455).