Wang Anzhao, Wei Zhicheng, Yuan Haolin, Zhu Yaxin, Peng Yu, Gao Zhenfei, Liu Yuenan, Shen Jinhong, Xu Huajun, Guan Jian, Yin Shankai, Liu Feng, Li Xinyi
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, China.
Front Neurosci. 2023 May 18;17:1170889. doi: 10.3389/fnins.2023.1170889. eCollection 2023.
Obstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the gene with OSA and OSA-related quantitative traits.
Four SNPs within the gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas.
In moderate-to-severe OSA patients, all four SNPs were positively associated with AHI, and rs9296158 showed the strongest association ( = 1.724, = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time ( = 0.0267, = 0.0254 and = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 - 1.575), = 0.019; OR (95% CI) = 1.294 (1.052 - 1.592), = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 - 1.575), = 0.047; OR (95% CI) = 1.281 (1.026-1.6), = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating , , and .
Single nucleotide polymorphisms in the gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.
阻塞性睡眠呼吸暂停（OSA）与精神疾病有关，尤其是抑郁症和创伤后应激障碍（PTSD）。先前已有报道称基因变异会增加患抑郁症和PTSD的风险。本研究旨在调查该基因中的单核苷酸多态性（SNP）与OSA及OSA相关定量性状之间的关联。
对5773名参与者进行该基因内4个SNP（rs1360780、rs3800373、rs9296158、rs9470080）的基因分型，并获取其人体测量数据和多导睡眠图数据。进行线性回归和逻辑回归分析，以评估该基因SNP与OSA相关性状之间的关系。采用二元逻辑回归评估SNP对OSA易感性的影响。基于3DSNP数据库评估SNP的相互作用基因，并采用SNP的表达定量性状位点（eQTL）分析来检验SNP与基因表达的相关性。借助脑图谱对人脑进行基因表达分析。
在中重度OSA患者中，所有4个SNP均与呼吸暂停低通气指数（AHI）呈正相关，且rs9296158的相关性最强（β = 1.724，P = 0.001）。进一步的分层分析表明，在中度OSA男性中，rs1360780、rs3800373和rs9470080与觉醒时间呈正相关（β分别为0.0267、0.0254和0.0043）。rs1360780和rs3800373处于更高等级的睡眠呼吸紊乱指数（MAI）类别的可能性分别高出28%和29.4%（OR（95%CI）= 1.280（1.042 - 1.575），P = 0.019；OR（95%CI）= 1.294（1.052 - 1.592），P = 0.015）。rs9296158和rs9470080使睡眠效率低下的风险分别增加25.7%和28.1%（OR（95%CI）= 1.257（1.003 - 1.575），P = 0.047；OR（95%CI）= 1.281（1.026 - 1.6），P = 0.029）。eQTL和基因表达模式的综合分析表明，4个SNP可能通过调节某些基因发挥作用。
该基因中的单核苷酸多态性与中重度OSA患者快速眼动（REM）睡眠期间的睡眠呼吸事件有关，且与中度OSA男性的睡眠结构变量有关。这些变异可能是睡眠障碍的潜在易感因素，尤其是在REM睡眠中。
