Novel susceptibility genes and biomarkers for obstructive sleep apnea: insights from genetic and inflammatory proteins

作者：Yang Zhao, Yinyin Jiang, Yaxi Wang, Haiying Zhang, Jun Zhu, Xu Jiang, Bo Shen, Yaning Chen, Dongfeng Li, Yang Pan, Feng Han, Li Zhang · 发表于：SLEEP · 年份：2024 · DOI：10.1093/sleep/zsae169 · 被引用次数：12 · 研究领域：Obstructive Sleep Apnea Research、Oral microbiology and periodontitis research、Sleep and related disorders

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, SH...