Circulating extracellular microRNAs as tissue-specific biomarkers of human health and disease.

Early pathological changes in many organ systems are difficult to detect, which creates challenges in disease prevention, diagnosis, and treatment. Here, we leverage circulating extracellular microRNAs (ex-miRNAs) to derive miRNA-based Tissue Signal (miR-TS) scores that simultaneously assess 17 tissues, including the brain, heart, liver, and lungs. Across three population-based cohorts and 10 clinical populations, miR-TS scores were robustly associated with relevant health outcomes with high tissue specificity. Using prospective data, miR-TS scores for the heart, brain, and lungs also functioned as predictive biomarkers that tracked the development of major health events, including acute myocardial infarction, cerebrovascular accidents, cognitive impairment, and airflow limitation. Finally, we demonstrated the utility of miR-TS scores in detecting tissue-specific toxicities from both acute and long-term exogenous exposures. Our results highlight the potential of circulating ex-miRNAs to function as robust biomarkers of tissue health and predict the onset of a wide range of diseases.