Date of Award
Doctor of Philosophy (PhD)
Computational Biology and Bioinformatics
Aging is the strongest risk factor for a number of diseases. Despite current risk prediction, prevention, and therapeutic strategies, age-related diseases including coronary artery disease (CAD), cancer, and now COVID-19, are the leading causes of death in the US and worldwide. The aging hematopoietic system is characterized by increased prevalence of acquired somatic variants predisposing to clonal expansion. Carriers of somatic mutations predisposing to clonal expansion in hematopoietic stem cells (clonal hematopoiesis of indeterminate potential, CHIP) are at increased risk for not only hematologic cancer but also atherosclerosis. Other classes of somatic variation besides CHIP, including larger somatic structural variants known as mosaic chromosomal abnormalities (mCAs), have also been identified to increase with age and increase risk of cancer. These data raise several unanswered questions. First, what other age-related diseases are associated with somatic mutations contributing towards clonal hematopoiesis such as CHIP and mCAs? Second, what inherited germline factors influence risk of acquired somatic variants? Third, how does the presence of CHIP influence DNA transcription in human blood cells? My dissertation addresses these questions by integrating genomic data across multiple cohorts with transcriptomic and deep phenotypic data.
Zekavat, Seyedeh Maryam, "Dissecting the Impact of Clonal Hematopoiesis on Age-Related Disease" (2022). Yale Graduate School of Arts and Sciences Dissertations. 685.