Extracellular RNAs in Relation to Cardiometabolic Risk

Blood Pressure, Obesity, Subclinical Atherosclerotic Cardiovascular Disease

Extracellular RNA, MicroRNA, Natural History

Background: Extracellular RNAs (exRNAs) send genetic data from cell to cell. This is how they affect the way cells communicate with each other. There are many types of exRNA, and they each serve different roles. But they have also been linked to some diseases. Researchers want to measure exRNAs to see how they relate to certain traits over time. They will use blood samples that were taken as part of the Framingham Heart Study (FHS). Objectives: To identify cross-sectional associations of exRNAs with age, sex, and cardiometabolic risk factors. Eligibility: People ages 30-70 who had blood taken as part of the FHS Third Generation cohort. Design: Researchers will study samples that have already been collected in the FHS. There will be no active participant contact for this project, only use of data that are collected as part of planned follow up from other studies. As part of the FHS, participants gave blood samples. They gave permission for the blood to be used for research. The exRNAs from the blood samples will be studied to see how they relate to certain traits. These include age, sex, and body mass index. The exRNAs will also be studied for their usefulness as biomarkers of risk for subclinical atherosclerotic cardiovascular disease. No study participants will be contacted for this study....

Extracellular RNAs (exRNAs) impact a wide range of biological processes and function to transfer genetic information between cells. In doing so, exRNAs affect cell-to-cell communications. Recent studies indicate that exRNAs are associated with a variety of diseases. Emerging data from elderly participants in the Framingham Heart Study (FHS) demonstrate that circulating levels of exRNA are correlated with several key traits including age, sex, and body mass index. Much more work is needed to determine the extent to which exRNAs are associated with a variety of clinically relevant traits across the age spectrum. We seek to measure a 665 exRNAs spanning a variety of classes in plasma from 4095 young to middle-aged adult participants in the Third Generation cohort of the FHS and to relate them to age, sex, and cardiometabolic risk factors (BMI, lipids, blood pressure, and fasting glucose) in cross-sectional analyses and to determine the relations of these exRNAs measured at baseline to serial changes in cardiometabolic risk factors during seven years of follow up. We also seek to relate exRNAs to subclinical atherosclerotic cardiovascular disease (ASCVD; assessed via multidetector CT measures of coronary artery calcium), and its progression during seven years of follow up. This grant application will establish an association of exRNAs with clinically relevant traits and diseases and will establish their utility as biomarkers of risk for cardiometabolic disease and subclinical ASCVD. To this end, we propose three aims: 1) To identify associations of exRNAs with age, sex, and cardiometabolic risk factors and subclinical ASCVD at a baseline examination, 2) To identify associations of exRNAs with longitudinal changes in cardiometabolic risk factors and subclinical ASCVD during seven years of follow up, and 3) To explore the genetic regulation of exRNAs via analysis of whole genome sequence data. We demonstrate that we have adequate power to detect associations of exRNAs with cardiometabolic risk factors and subclinical atherosclerosis at baseline and with their longitudinal change during follow up.

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