Clonal hematopoiesis (CH) is defined by the presence of shared acquired genetic mutations in a large fraction of blood cells. CH is a common phenomenon in the elderly. Presence of CH is associated with a higher risk of blood cancer, mortality, and a wide range of diseases, including cardiovascular, pulmonary, and liver diseases.
We and others have identified genes that are recurrently mutated in CH. These genes are also commonly mutated in blood cancer. Recent studies have revealed that the majority of CH do not harbor mutations in previously known genes. Moreover, the mechanisms of how CH develops and leads to diseases are not understood.
This project aims to identify new genetic alterations in CH and discover mechanisms influencing CH and the pathogenesis of CH-mediated diseases. The massive sample size and coverage of the sequencing data in UK Biobank provides opportunities to identify new genetic variations and regulators of CH and their implications on human health. We will utilize sequencing data from approximately half a million participants in the UK Biobank to
1) characterize genetic mutations involved in CH,
2) identify genetic and environmental factors that influence the risk of developing CH, and
3) develop methods to predict risks associated with CH mutations.
This project will identify several new genetic alterations in CH and reveal novel mechanisms of CH development. These findings may provide opportunities for a) stratifying risk, b) early diagnosis, and c) develop new therapies for treating CH-mediated diseases. The genetic alterations identified here may serve as markers for screening of CH in the longer run. The findings will be shared with other researchers and published in scientific journals and meetings.
