Clonal haematopoiesis of indeterminate potential (CHIP) refers to the phenomenon in which mutations occur in ageing haematopoietic stem cells (HSCs), resulting in clonal selection and expansion. CHIP was defined by the presence of white cells in peripheral blood carrying the characteristic CHIP mutations with a variant allele fraction (VAF) greater than 2%. It is now becoming clear that CHIP is associated with a pro- inflammatory state and increased risks for haematological malignancies and cardiovascular and cerebrovascular diseases (1, 2). Reportedly, the prevalence of CHIP mutation increases with age, occurring in 10% of people over 70 years old and 20% of those over 90 years old (3). Furthermore, it is unclear how specific CHIP mutations, singly or in combination, are associated with specific complications. Such information may form the foundation for Personalized Disease Prevention (PDP) for the ageing population.
The purpose of this project is to find the association of clonal haematopoiesis of indeterminate potential (CHIP) mutations with specific clinical complications based on genetic and clinical data derived from UK Biobank.
Specific objectives of the project are:
1) Evaluate association of specific CHIP mutations with clinical phenotypes.
2) Examine how the presence of two or more CHIP mutations affect clinical phenotypes.
References:
1. Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, et al. Clonal Hematopoiesis and Risk of
Atherosclerotic Cardiovascular Disease. N Engl J Med 2017 Jul 13; 377(2): 111-121.
2. Xie M, Lu C, Wang J, McLellan MD, Johnson KJ, Wendl MC, et al. Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nat Med 2014 Dec; 20(12): 1472-1478.
3. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV, Mar BG, et al. Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 2014 Dec 25; 371(26): 2488-2498.