A Clinical Atlas for Phenome-Wide Association Study of Obstructive Sleep Apnea Across Electronic Health Record Domains

Obstructive sleep apnea (OSA) is a heterogeneous disorder whose associations across the entire phenome remain incompletely characterized by hypothesis-driven outcome-specific analyses. We constructed a multidomain atlas for phenome-wide association study of OSA in 222,109 adults undergoing diagnostic sleep testing in Kaiser Permanente Southern California. Using apnea-hypopnea index, we examined cross-sectional associations across diagnoses, laboratory tests, medications, procedures, healthcare utilization, behaviors, and symptoms; associations with incident diseases; and data-driven cross-domain phenotypes. After full adjustment, 169 prevalent phecodes and 16 incident phecodes remained Bonferroni-significant. Positive associations converged most consistently on cardiometabolic diseases, including hypertension, impaired glucose metabolism, hyperlipidemia, obesity, and heart failure, with concordant laboratory, medication, and cardiac-measurement signals. Multidimensional physiologic, symptom, and comorbidity phenotypes showed heterogeneous disease incidence after adjustment, with patterns not aligned with apnea-hypopnea index severity alone. These findings define the broad clinical landscape of OSA and provide a comprehensive atlas for replication and hypothesis generation.