Risk factors and long-term health impacts of genetically determined clonal hematopoiesis
Approved Research ID: 86473
Approval date: August 10th 2022
Age-related clonal hematopoiesis (CH), defined as the expansion of blood-cell clones caused by somatic mutations, is common among older persons. CH is associated with increased risks of hematological tumors and cardiovascular diseases. CH events were defined by large-scale chromosomal alterations or small mutations in known CH driver genes, two different ways to identify CH. However, it is largely unknown whether small mutations and large-scale chromosomal alterations can jointly contribute to the development of CH and the underlying biological mechanisms. Besides, growing evidence has shown that CH events might occur in the absence of previous well-known driver genes, indicating further investigations are wanted for CH events that occur outside the existing genes.
By analyzing the abundantly available genome and phenotype data from the UKB cohort in the next three years, we aim to (1) assess the potential interaction effects between small gene mutations and chromosomal alterations on the development of CH; (2) find mutations that have not been listed in the previous well-known CH driver mutations and assess the associations of these genes with CH events; (3) compare different approaches for the identification of CH events and find the most clinically meaningful method to characterize CH events; (4) further explore the potential determinants and long-term health outcomes of CH events. We believe these findings will facilitate CH identification and enable a better understanding of population-based CH distribution and its causes and consequences.