Longitudinal Impact of Clonal Hematopoiesis on Aging Outcomes and Risk Prediction in the REasons for Geographic and Racial Differences in Stroke Study

About This Grant

PROJECT SUMMARY Clonal hematopoiesis (CH) refers to abnormal expansion of hematopoietic cell clones in the absence of hematologic abnormalities. Though CH was initially identified as recurrent somatic mutations in those with myeloid malignancies, these mutations are identified in apparently healthy individuals and are especially common in older individuals. Clonal hematopoiesis has only been recognized as an entity for the past ~10 years, and we have a poor understanding of the risk factors for, evolution of, and consequences of CH in a broad representative population. We propose to measure CH in the 30,239 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study at baseline and ~9 years later. By measuring CH over time, we will gain insights into clonal dynamics and how CH changes over time as well as potential driving factors for CH which may be amenable to interventions. Our aims are to: 1. Define the baseline risk factors of CH in the REGARDS cohort including germline genetics. 2. Prospectively define the risk factors for CH incidence and progression in the REGARDS cohort 3. Establish the contribution and causality of CH to adverse age-related outcomes including survival, cognition, coronary heart disease, stroke, heart failure, cancer, and incident cardiovascular risk factors. The biracial and geographically diverse REGARDS cohort offers an unrivaled opportunity to determine novel insights into the etiology, epidemiology, and consequences of CH.