Abstract

Implementation of electronic health record biobanks has facilitated linkage between clinical and questionnaire data and enabled assessments of relationships between sleep health and diseases in phenome-wide association studies (PheWAS). In the Mass General Brigham Biobank, a large health system-based study, we aimed to systematically catalog associations between time in bed, sleep timing, and weekly variability with clinical phenotypes derived from ICD-9/10 codes. Self-reported habitual bed and wake times were used to derive variables: short (<7 hours) and long (≥9 hours) time in bed, sleep midpoint, social jetlag, and sleep debt. Logistic regression and Cox proportional hazards models were used to test cross-sectional and prospective associations, respectively, adjusted for age, gender, race/ethnicity, and employment status and further adjusted for body mass index. In cross-sectional analysis (n = 34,651), sleep variable associations were most notable for circulatory system, mental disorders, and endocrine/metabolic phenotypes. We observed the strongest associations for short time in bed with obesity, for long time in bed and sleep midpoint with major depressive disorder, for social jetlag with hypercholesterolemia, and for sleep debt with acne. In prospective analysis (n = 24,065), we observed short time in bed associations with higher incidence of acute pain and later sleep midpoint and higher sleep debt and social jetlag associations with higher incidence of major depressive disorder. Our analysis reinforced that sleep health is a multidimensional construct, corroborated robust known findings from traditional cohort studies, and supported the application of PheWAS as a promising tool for advancing sleep research. Considering the exploratory nature of PheWAS, careful interrogation of novel findings is imperative.

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