An extensive new study from Amgen subsidiary deCODE genetics, which was published in Nature Genetics today, sheds light on the somatic and germline genetics of clonal hematopoiesis as well as its epidemiology. Utilising a novel somatic mutation Barcoding technique in conjunction with whole genome sequence data from Iceland and the UK Biobank, clonal hematopoiesis was examined at the population level.
A situation known as clonal hematopoiesis occurs when a single clonal lineage of hematopoietic stem cells (HSC) proliferates and provides a significant fraction of adult blood cells. The deCODE researchers identified clonal hematopoiesis in over 16,000 participants by analysing whole-genome sequence data from over 176,000 individuals. The study confirmed that clonal hematopoiesis is about 50% in individuals over 80 years of age, which is a fairly typical occurrence in the elderly. Individuals with clonal hematopoiesis have greater mortality rates and a higher chance of receiving a subsequent diagnosis of haematological neoplasia.
It has previously been suggested that clonal hematopoiesis has a role in a wide range of nonhematological disorders, from cardiovascular disease to cancer. The results of the study demonstrated that smoking has a dose-dependent effect on the rate at which clonal hematopoiesis develops and that smoking is probably linked to all associated nonhematological disorders. The investigation discovered evidence of HSC mutations that can promote clonal proliferation. Additionally, the researchers discovered 25 hereditary sequence changes that make people more likely to experience clonal hematopoiesis.
Using whole genome sequencing, the deCODE scientists created a technique for identifying clonal hematopoiesis. This technique is based on the observation that each clone has its own distinct “barcode” of mutations that occurred somatically during development and were present in the founder cell at the time the clone was created. Sequencing can identify this barcode of mutations and determine whether an individual has clonal hematopoiesis if a certain HSC clone grows to a suitable size.
Numerous indicators of a premalignant growth of cell clones with the potential to develop into cancer are present in clonal hematopoiesis. It is true that clonal hematopoiesis increases the risk of early death and haematological neoplasia. Remarkably, a large portion of the increased mortality could be ascribed to smoking-related illnesses, even though haematological neoplasia was responsible for part of it. It has been discovered that clonal hematopoiesis raises the chance of developing hematopoietic neoplasia, chronic obstructive pulmonary disease, lung cancer, peripheral artery disease, emphysema, and alcoholism.
However, the study found no evidence to support the commonly believed link between cardiovascular disease and clonal hematopoiesis. It was discovered that smoking affected clonal hematopoiesis in a dose-dependent manner and that it most likely quickens as people age. This implies that nonhematological illness connections are primarily the consequence of smoking behaviour and advanced age, and that clonal hematopoiesis is in some ways a smoking signal.
After that, the study looked into the genetic foundations of clonal hematopoiesis, initially concentrating on mutations that could happen in HSCs and provide them a selective advantage that enables them to seize control of bone marrow and hematopoiesis. Several of these so-called driver mutations are discovered by them; numerous of these have been linked to myeloid and lymphoid neoplasia. The majority of HSC clones, however, lack a clear driver mutation, and it is still unknown why they proliferate. By focusing on hereditary variations that make individuals more likely to develop CH, deCODE discovered changed genes at 25 of these loci.
In several cases, it was demonstrated that these variations had an impact on the amounts of plasma proteins linked to CH, splicing, or gene expression. Leukocyte telomere length, myeloproliferative neoplasia, and blood cell counts are frequently impacted by the variations. All things considered, the research has shed significant light on the genetics and epidemiology of clonal hematopoiesis.
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