阻塞性睡眠呼吸暂停的新型易感基因和生物标记物：遗传和炎症蛋白的启示。

IF 5.6 2区医学 Q1 Medicine

Sleep Pub Date : 2024-08-01 DOI:10.1093/sleep/zsae169

Yang Zhao, Yinyin Jiang, Yaxi Wang, Haiying Zhang, Jun Zhu, Xu Jiang, Bo Shen, Yaning Chen, Dongfeng Li, Yang Pan, Feng Han, Li Zhang

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引用次数: 0

摘要

研究目的：许多观察性研究发现阻塞性睡眠呼吸暂停（OSA）与炎症蛋白有关，但这些关联的方向性仍不明确。因此，我们旨在阐明基因预测的炎症蛋白与 OSA 的潜在关联：方法：基于全基因组关联研究数据，我们应用孟德尔随机化（MR）方法探讨了循环炎症蛋白与 OSA 之间的潜在联系，主要使用了反方差加权法以提高稳健性。我们还使用了Cochran's Q检验、MR-Egger截距检验、MR-PRESSO和leave-one-out方法来进行多向性和异质性的敏感性检验。使用其他独立数据进行了复制分析和荟萃分析。Steiger检验和多变量MR评估了暴露因素的独立影响，功能图谱和注释（FUMA）平台用于识别关键基因，以加深对遗传学的理解：结果：我们的研究发现了 21 种与 OSA 相关表型显著相关的循环炎症蛋白。值得注意的是，IL-10RA、IL-18R1、TNFSF14、CCL23、ADA 和 SLAMF1 对多种表型有显著影响。经过FDR校正，IL-18R1、SLAMF1、IL-10RA和IL-17C被确定为OSA的重要候选因子，多变量MR分析加强了20个炎症因子的独立遗传性。FUMA 平台发现了七个重叠基因：ROBO1、PRIM1、NACA、SHBG、HSD17B6、RBMS2 和 WWOX。所有反向 MR 分析和敏感性分析都证实了这些关联的稳健性：我们的研究结果强调了炎症蛋白与 OSA 发病机制之间的重要关联，揭示了新的相关性和易感基因。这些发现推动了 OSA 风险生物标志物的鉴定，并强调了遗传和炎症特征在 OSA 管理中的重要性。

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Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

Study objectives: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA.

Methods: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics.

Results: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations.

Conclusions: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

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来源期刊

Sleep Medicine-Neurology (clinical)

CiteScore

8.70

自引率

10.70%

发文量

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