Leveraging a Unique existing Cohort to elucidate the Link between sleep and cardio-metabolic disease

Despite current evidence-based treatments for cardiovascular and metabolic diseases (CMD), these disease remain highly prevalent and a leading cause of death. Therefore, identifying new disease mechanisms is paramount to further reduce or prevent CMD. Moreover, there are large racial disparities in CMD in the US such that minority groups, particularly African Americans, experience a greater burden of disease. Among potential CMD risk factors, the importance of inadequate sleep is gaining recognition. In this project, we will capitalize on a large, on-going family-based study in Brazil that has collected genetic, metabolomic and cardiometabolic data. The primary objective of this project is to examine detailed measures of sleep and their associations with biomarkers of CMD, to assess whether sleep is associated with race, genetic ancestry, and social disparity, and to identify transcriptional and metabolic pathways as potential mechanisms to explain the effects of sleep on CMD development. Accumulating data suggest that specific EEG-based characteristics of sleep, such as slow-wave sleep (SWS) or slow-wave activity (SWA; EEG spectral power in the 0.5-4 Hz range), are highly heritable traits that may be drivers of subclinical cardiac and metabolic disease acting through the pleiotropic modulation of several risk factors. Furthermore, sleep duration, quality and SWS are reduced in African Americans compared to whites, raising questions about the degree to which sleep mediates racial health disparities. Current research has not fully explored the relationship between SWS/SWA and CMD, nor does it address the unknown underlying mechanisms. Therefore, the current proposal aims to fill this gap in knowledge by adding PSG to an existing study with 2,000 participants aged 18 to 90 years. We hypothesize: 1) that less SWS/SWA is associated with increased CMD risk, including higher fasting glucose and estimated insulin resistance (HOMA), higher hemoglobin A1c and chronic inflamm