Cade Brian E, Li Le, Duff Megan, Yang Chen, Hassan Syed Moin, Yu Xinting, Goodman Matthew O, Alex Raichel M, Azarbarzin Ali, Batool-Anwar Salma, Nezami Farhad R, Ramezani Amin, Sands Scott A, Wang Heming, Kirchner H Lester, Shah Neomi A, Epstein Lawrence J, Pavlova Milena K, Redline Susan
Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115, USA.
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
medRxiv. 2025 Aug 1:2025.07.30.25332466. doi: 10.1101/2025.07.30.25332466.
Obstructive sleep apnea (OSA) is associated with a wide range of comorbidities, but large-scale phenome-wide analyses in clinical biobanks remain under-reported. In this study, we identified common comorbidities enriched in patients with OSA, tested the temporality of these associations, and analyzed relevant associations with summary sleep recording data.
48,251 participants with OSA in the Mass General Brigham healthcare system were identified using a natural language processing phenotyping algorithm and/or evidence of an elevated apnea-hypopnea index (AHI). Controls were matched (2:1) on demographics, body mass index (BMI), and healthcare utilization. Associations with 358 incident and 563 cross-sectional diseases were tested using Modified Poisson regression, adjusting for covariates. Sensitivity analyses examined timing by binning data in years relative to the first OSA diagnosis. Selected laboratory results were obtained based on associated diseases. Associated diseases were tested with sleep recording statistics (n ≤18,348).
179 incident and 421 cross-sectional diseases were associated with OSA at Bonferroni significance. 37 diseases had Bonferroni-significant sex interactions. Several associations were significant years before the first recorded OSA diagnosis. Four red blood cell laboratory measures were significant ten years prior to the first diagnosis. One incident and 47 cross-sectional diseases were associated with the AHI and/or chronic hypoxemia.
Obstructive sleep apnea is associated with enrichment of hundreds of diseases, several of which are supported by orthogonal polysomnographic evidence. Leveraging early signs of OSA in clinical data may help to identify at-risk patients.
阻塞性睡眠呼吸暂停（OSA）与多种合并症相关，但临床生物样本库中大规模的全表型分析报道仍较少。在本研究中，我们确定了OSA患者中富集的常见合并症，测试了这些关联的时间顺序，并分析了与睡眠记录汇总数据的相关关联。
使用自然语言处理表型算法和/或呼吸暂停低通气指数（AHI）升高的证据，在麻省总医院布莱根医疗系统中识别出48251名OSA参与者。根据人口统计学、体重指数（BMI）和医疗保健利用率对对照组进行匹配（2:1）。使用修正泊松回归测试与358种新发疾病和563种横断面疾病的关联，并对协变量进行调整。敏感性分析通过对相对于首次OSA诊断的年份数据进行分组来检查时间顺序。根据相关疾病获得选定的实验室结果。使用睡眠记录统计数据（n≤18348）对相关疾病进行测试。
在Bonferroni显著性水平下，179种新发疾病和421种横断面疾病与OSA相关。37种疾病存在Bonferroni显著性的性别交互作用。在首次记录的OSA诊断前数年，有几种关联具有显著性。四项红细胞实验室指标在首次诊断前十年具有显著性。一种新发疾病和47种横断面疾病与AHI和/或慢性低氧血症相关。
阻塞性睡眠呼吸暂停与数百种疾病的富集相关，其中几种得到了多导睡眠图正交证据的支持。利用临床数据中OSA的早期迹象可能有助于识别高危患者。
