Abstract
BACKGROUND: Insufficient physical activity (PA) is associated with higher risk of morbidity and premature mortality. Wearable devices offer a scalable, objective measurement of physical activity, but most studies reduce these data to a single activity metric measured over a fixed 7-day period. We compared different wearable-derived phenotyping approaches to understand their impact on activity-disease associations. METHODS: We analyzed 11 million days of Fitbit data from 29,351 participants in the All of Us Research Program, deriving four daily activity metrics (step count, peak 1-min cadence, peak 30-min cadence, and heart rate per step) across five time-windows (1-day, 1-week, 1-month, 6-months, 1-year). We performed phenome-wide analyses on >700 incident and >1,300 prevalent disease outcomes identified from linked electronic health records. FINDINGS: Among participants with EHR and Fitbit data (mean age 57.3 years, 69% female, 47% with >1 year of Fitbit data), all 20 phenotypes were highly correlated (median Pearson r = 0.71). Longer measurement windows yielded stronger and more stable associations, with 1-year step count associated with 373 prevalent and 37 incident outcomes (versus 231 and 17 for 1-day step count) after Bonferroni-correction, including novel associations with chronic pain syndrome, SARS-CoV-2, and autoimmune disease. Differences between prevalent and incident associations suggest that activity metrics can act as both early markers of disease or risk factors. INTERPRETATION: These findings highlight how large-scale, longitudinal wearable data can advance understanding of health and disease and inform scalable approaches for clinical risk stratification. FUNDING: National Institutes of Health Intramural Research Program, Wellcome Trust.