Nature and Science of Sleep (Jun 2024)

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

  • Chen Z,
  • Zeng J,
  • Pei X,
  • Zhao J,
  • Zhao F,
  • Zhang G,
  • Liang K,
  • Li J,
  • Zhao X

Journal volume & issue
Vol. Volume 16
pp. 787 – 800

Abstract

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Zhengjie Chen,1,2,* Jinjie Zeng,3,* Xiang Pei,1,2 Jingjing Zhao,1,2 Fang Zhao,1,2 Guoxin Zhang,1,2 Kexin Liang,1,2 Jiarong Li,2 Xiaoyun Zhao1,2,4,5 1Clinical School of Thoracic, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Respiratory & Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 3Department of Respiratory, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 4Department of Respiratory & Critical Care Medicine, Chest Hospital of Tianjin University, Tianjin, People’s Republic of China; 5DeepinBreath Union Laboratory, Tianjin Chest Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyun Zhao, Department of Respiratory & Critical Care Medicine, Tianjin Chest Hospital, No. 261 Taierzhuang South Road, Jinnan District, Tianjin, People’s Republic of China, Email [email protected]: 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

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