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

Abstract

Lian Weng,1– 3,* Xiongjunjie Luo,1– 3,* Yuxi Luo,1– 3 Qian Zhang,1– 3 Kaitao Yao,1– 3 Junjie Tan,1– 3 Yiran Yin1– 3 1Department of orthopedics, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Sichuan Provincial Laboratory of Orthopedic Engineering, Luzhou, Sichuan Province, 646000, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiran Yin, Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, No. 25 Tai Ping Street, Jiang Yang District, Luzhou, Sichuan Province, 646000, People’s Republic of China, Tel [phone], Email [email protected]: 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

Keywords

• sleep apnea syndrome osteoarthritis mendelian randomization bioinformatics