Li Juan, Lv Qianwen, Sun Haili, Yang Yunyun, Jiao Xiaolu, Yang Song, Yu Huahui, Qin Yanwen
Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, People's Republic of China.
Emergency Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China.
Nat Sci Sleep. 2022 Mar 3;14:363-372. doi: 10.2147/NSS.S343205. eCollection 2022.
Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population.
This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (, and ), from which each individual's PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples.
The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393-5.955, = 0.004) and 5.402-fold (95% CI: 2.311-12.624, <0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, = 0.02).
Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.
阻塞性睡眠呼吸暂停（OSA）是一种常见的慢性多基因疾病。全基因组关联研究已鉴定出多个与OSA相关的基因标记。在此，我们旨在构建一个多基因风险评分（PRS），并在中国汉族人群中研究其与OSA存在情况的关联。
本研究纳入了1057名个体，对来自三个基因（、和）的九个易感位点进行基因分型，通过累加风险等位基因的数量计算每个个体的PRS。通过逻辑回归分析确定PRS与OSA之间的关联。使用1000次重采样的自助法通过受试者工作特征（ROC）曲线评估模型辨别能力。
受试者包括874例OSA患者和183例对照。较高的PRS与呼吸暂停低通气指数（AHI）增加相关。PRS是OSA发生的重要危险因素（每标准差OR = 1.237，= 0.030）。与遗传风险较低的个体相比，PRS较高的个体患OSA和中重度OSA的风险分别高2.88倍（95% CI：1.393 - 5.955，= 0.004）和5.402倍（95% CI：2.311 - 12.624，<0.001）。更重要的是，与仅基于临床因素确定风险相比，加入PRS提高了对OSA（AUC从）和中重度OSA（AUC从）的辨别准确性（分别为0.75至0.78，= 0.02；0.80至0.83，= 0.02）。
我们的研究表明，PRS与AHI和OSA独立相关。将PRS与传统危险因素相结合可提高对OSA的辨别能力。 （注：原文中部分基因名称未给出具体内容，翻译时保留原文形式）
