| dc.description.abstract | Clonal hematopoiesis (CH) is a common age-related condition characterized by an acquired somatic mutation in a hematopoietic stem cell that confers a growth advantage. Patients with CH have an increased risk of numerous conditions including blood cancer, cardiovascular disease, and death. Individuals with CH who have clones that make up a larger proportion of their blood have worse outcomes, but little is known about what factors increase the rate of clonal expansion. The ability to identify individuals whose clones will grow at a faster rate, and who are therefore more likely to progress to large clones and adverse outcomes, is crucial for advancing clinical management of CH. Leveraging large-scale biobanks and longitudinal studies, I identified somatic genetic, germline genetic, epigenetic, and environmental factors that are associated with CH expansion rate and empirically demonstrate for the first time that faster clonal growth is associated with worse outcomes. My work identifies specific biological pathways that may be amenable to therapeutic intervention in patients with CH. My findings also provide a roadmap for advancing precision medicine in the clinical management of patients with CH through improved prognostication of clone trajectory. | |
