Abstract
Rest-activity rhythm and sleep may serve as potential intervention targets for a variety of diseases. However, the underlying biological mechanisms of rest-activity rhythm, sleep, and their proteomic associations with multiple diseases remain largely unexplored. Here, using data from approximately 10 000 participants in the UK Biobank with accelerometer-derived measures and proteomics profiles, we characterized the proteomic signatures of rest-activity and sleep and explored their associations with health outcomes. We found that the proteins associated with rest-activity and sleep were mainly enriched in inflammation, immune response and complement system. Most rest-activity and sleep measures, along with their associated proteomic signatures, were significantly associated with incident diabetes, cardiovascular disease, chronic kidney disease, respiratory diseases, and extended life expectancy. Several proteins, such as ADM and CA14, were observed to mediate multiple associations across distinct rest-activity and sleep measures. The impact of rest-activity and sleep measures on chronic diseases and mortality may be mediated through diverse biological pathways involving multiple proteins. These findings reveal potential mechanisms underlying these complex relationships and provide novel insights for the development of targeted intervention strategies.