Clonal hematopoiesis (CH) is a pre-malignant condition in blood. CH, defined by somatic genetic variants in the blood cells of healthy individuals, is common in the elderly. CH is associated with a higher risk of blood cancer, mortality, and age-related chronic diseases, including cardiovascular diseases. Although a number of CH driver genes and variations are known, the driver variants in most CH clones are unknown. Moreover, the mechanisms underlying the development of CH and transformation to cancer are not well understood. This project aims to study the landscape of driver genetic variations in CH and identify regulators of CH development. For this, we will utilize the exome and genome sequencing data from solid tumor patients. In cancer genomic projects, paired tumor and normal samples are sequenced. Blood samples are most often used as normal samples. In this project, we will utilize the sequencing data from blood samples of solid tumor patients to identify blood-specific somatic variations. We will utilize tumor sequencing data as controls to filter out artifacts and germline variants. Using these paired data, we will identify high-quality somatic variations in the blood. The genetic variants will then be used to identify new drivers of CH and to perform genetic association studies and mutational signature analysis. The high-quality genetic variants will also allow benchmarking our workflows to detect somatic variations when paired samples are unavailable. In summary, this project will facilitate the identification of new genetic drivers of CH and facilitate methodological improvements for the study of CH.