循环炎症蛋白与阻塞性睡眠呼吸暂停之间的因果关系：一项双向孟德尔随机化研究

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

作者信息

Chen Zhengjie, Zeng Jinjie, Pei Xiang, Zhao Jingjing, Zhao Fang, Zhang Guoxin, Liang Kexin, Li Jiarong, Zhao Xiaoyun

机构信息

Clinical School of Thoracic, Tianjin Medical University, Tianjin, People's Republic of China.

Department of Respiratory & Critical Care Medicine, Tianjin Chest Hospital, Tianjin, People's Republic of China.

出版信息

Nat Sci Sleep. 2024 Jun 13;16:787-800. doi: 10.2147/NSS.S458637. eCollection 2024.

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.

目的

临床研究已证实阻塞性睡眠呼吸暂停（OSA）的发病及进展与炎症级联反应的激活之间存在复杂关联。本研究通过应用孟德尔随机化（MR）技术，深入探究91种循环炎症蛋白（CIPs）与OSA之间的因果关系。

方法

利用来自芬兰生物银行（FinnGen）欧洲人群全基因组关联研究（GWAS）的OSA基因数据，以及来自14824名欧洲参与者的CIPs汇总水平GWAS数据，我们进行了一项双向MR研究。

结果

本研究表明，若干因素可能与OSA风险相关。白细胞介素-17C（优势比（OR）=1.090，p=0.0311）、趋化因子配体25（CCL25，OR=1.079，p=0.0493）、成纤维细胞生长因子-5（FGF-5，OR=1.090，p=0.0003）、CD5（OR=1.055，p=0.0477）和肿瘤坏死因子配体超家族成员14（TNFSF14，OR=1.092，p=0.0008）可能与OSA风险呈正相关。相反，白细胞介素-20受体A（IL-20RA，OR=0.877，p=0.0107）、CCL19（OR=0.933，p=0.0237）、巨噬细胞炎性蛋白-1α（MIP-1α，OR=0.906，p=0.0042）、Flt3配体（Flt3L，OR=0.941，p=0.0019）、胱抑素T5（CST5，OR=0.957，p=0.0320）、骨保护素（OPG，OR=0.850，p=0.0001）和肿瘤坏死因子相关凋亡诱导配体（TRAIL，OR=0.956，p=0.0063）可能降低OSA风险。此外，观察到OSA导致白细胞介素-10受体A（IL-10RA）水平升高（OR=1.153，p=0.0478）。相反，OSA可能导致CCL28（OR=0.875，p=0.0317）、神经源分化因子（DNER，OR=0.874，p=0.0324）、FGF-21（OR=0.846，p=0.0344）和集落刺激因子-1（CSF-1，OR=0.842，p=0.0396）水平降低。