Distinguishing Age-specific Patterns in Comorbidities of Obstructive Sleep Apnea Using Real-World Data.

Obstructive sleep apnea (OSA) is associated with a wide range of comorbidities, but the extent to which these follow predictable, age-dependent patterns is not well understood. Identifying such patterns could provide insight into OSA heterogeneity and its links to physiological measures of OSA. We trained age-dependent topic models (ATM) on longitudinal electronic health records from 36,426 patients with OSA in the Mass General Brigham Biobank. ATM organizes incident diagnoses into distinct comorbidity "topics," whose age-specific disease loadings represent predictive patterns linking related diagnoses across the life course. We applied the trained model to compute individual-level topic scores in independent data: a cohort of 11,689 OSA cases and 22,695 matched controls, and a cohort of 6,220 patients with polysomnography (PSG)-derived physiological measures. We identified 19 distinct age-dependent comorbidity profiles, all significantly associated with OSA case status (FDR-adjusted p<0.05). Topics reflected recognizable clusters including metabolic, neuropsychiatric, and immune-mediated conditions, and several were distinguished by age-of-onset of key comorbidities, such as early- vs late-onset asthma. Seventeen of the 19 topics were significantly associated with at least one of 13 PSG-derived physiological measures, including associations between cardiometabolic topics and the apnea-hypopnea index, sleep apnea specific hypoxic burden, and respiratory event-specific heart rate burden. These findings indicate that age-dependent comorbidity patterns distinguish meaningful OSA subtypes with differing prognoses and endophenotype associations. ATM offers insight into complex OSA comorbidity and suggests that age-informed, topic-based stratification may improve individualized risk assessment, interpretation of PSG findings, and targeting of clinical interventions.