Plasma Proteomic Signatures of Accelerometer-Measured Sedentary Behavior Are Associated with Future Disease Risk

Previous studies have shown the link between sedentary behavior and health outcomes. However, self-reported sedentary behavior is less accurate than accelerometer-measured sedentary behavior. Additionally, the proteomic signatures associated with sedentary behavior and their potential impact on biological pathways remain unknown. In this study, we identified proteomic signatures of sedentary behavior using whole-proteome association analysis and LASSO regression based on data from 2921 plasma proteins in 10,848 participants with complete accelerometer measurements from the UK Biobank. Our results indicate that both sedentary behavior and its related proteomic signatures are significantly linked to the risk of developing diabetes, hypertension, and chronic kidney disease. Furthermore, mediation analysis showed that proteomic signatures of sedentary behavior mediate the relationships between sedentary activity and the risk of diabetes and chronic kidney disease. These findings suggest that sedentary behavior and its associated proteomic signatures contribute to increased risks of these diseases. Investigating how sedentary behavior affects diseases through peripheral physiology is essential for public health.