Germline risk of clonal haematopoiesis

Nat Rev Genet. 2021 Sep;22(9):603-617. doi: 10.1038/s41576-021-00356-6. Epub 2021 May 13.

Abstract

Clonal haematopoiesis (CH) is a common, age-related expansion of blood cells with somatic mutations that is associated with an increased risk of haematological malignancies, cardiovascular disease and all-cause mortality. CH may be caused by point mutations in genes associated with myeloid neoplasms, chromosomal copy number changes and loss of heterozygosity events. How inherited and environmental factors shape the incidence of CH is incompletely understood. Even though the several varieties of CH may have distinct phenotypic consequences, recent research points to an underlying genetic architecture that is highly overlapping. Moreover, there are numerous commonalities between the inherited variation associated with CH and that which has been linked to age-associated biomarkers and diseases. In this Review, we synthesize what is currently known about how inherited variation shapes the risk of CH and how this genetic architecture intersects with the biology of diseases that occur with ageing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / pathology*
  • Clonal Hematopoiesis*
  • Germ Cells / metabolism*
  • Humans
  • Mutation*