Reykjavik, ICELAND,
Nov. 6, 2023 /PRNewswire/ -- A
comprehensive new study from deCODE genetics, a subsidiary of
Amgen, published today in Nature Genetics, provides insights into
the epidemiology and somatic and germline genetics of clonal
hematopoiesis. Whole genome sequence data from Iceland and the UK Biobank, combined with a
unique somatic mutation Barcoding strategy, was used to investigate
clonal hematopoiesis at the population scale.
Clonal hematopoiesis is a condition that arises when a single
clonal lineage of hematopoietic stem cells (HSC) expands and
becomes the source of a substantial proportion of mature blood
cells. The deCODE scientists used whole-genome sequence data from
over 176,000 people to detect clonal hematopoiesis in more than
16,000 subjects. The study reaffirmed that clonal hematopoiesis is
very common in the elderly, approaching 50% in people over 80 years
old. People with clonal hematopoiesis have an increased risk of
being diagnosed subsequently with hematological neoplasia, and they
have higher mortality rates. Clonal hematopoiesis had previously
been claimed to be involved in a broad spectrum of nonhematological
conditions ranging from carcinomas to cardiovascular disease. The
study showed that smoking accelerates the development of clonal
hematopoiesis in a dose-dependent manner and that all the
associated nonhematological diseases are likely tied to smoking
behaviour. The study found evidence of mutations that occur in HSC
that can drive their clonal expansion. Moreover, the investigators
found 25 inherited sequence variants that predispose individuals to
develop clonal hematopoiesis. The deCODE scientists developed a
method for detecting clonal hematopoiesis based on whole genome
sequence. This method relies on the fact that every clone carries a
unique "barcode" of mutations that arose somatically during
development and were present in the founder cell at the inception
of the clone. If a particular HSC clone expands sufficiently, then
this barcode of mutations can be detected by sequencing and
provides an indicator that the subject has clonal hematopoiesis.
Clonal hematopoiesis has many of the hallmarks of a premalignant
expansion of cell clones with a potential to become cancerous.
Indeed, people with clonal hematopoiesis are at increased risk of
hematological neoplasia and early death. Surprisingly, while some
of the increased mortality was due to hematological neoplasia, much
of it could be attributed to smoking-related diseases. Clonal
hematopoiesis was found to increase risk of being diagnosed with
not only hematological neoplasia, but also chronic obstructive
pulmonary disease, lung cancer, peripheral artery disease,
emphysema and alcohol abuse. The study did not, however, find
evidence supporting the widely reported association of clonal
hematopoiesis and cardiovascular disease. Smoking was found to have
a dose-dependent effect on clonal hematopoiesis and probably
accelerates its development as people age. This suggests that
clonal hematopoiesis is in some respects a smoking marker and that
nonhematological disease associations are essentially a result of
smoking behaviour and advanced age. The study then investigated the
genetic underpinnings of clonal hematopoiesis, focusing first on
mutations that might occur in the HSCs, giving them a selective
advantage allowing them to take over the bone marrow and
hematopoiesis. They find several of these so-called driver
mutations, many of which have known involvement in myeloid and
lymphoid neoplasia. However, most HSC clones do not have an obvious
driver mutation and why they expand remains a mystery. Turning to
inherited variants that predispose people to getting CH, deCODE
found altered genes at 25 such loci. These variants were in some
instances shown to affect gene expression, splicing or levels of
plasma proteins connected with CH. The variants tend to also affect
blood cell counts, myeloproliferative neoplasia and leukocyte
telomere length. Overall, the study has provided substantial
insights into the genetics and epidemiology of clonal
hematopoiesis.
Based in Reykjavik, Iceland,
deCODE is a global leader in analyzing and understanding the human
genome. Using its unique expertise and population resources, deCODE
has discovered genetic risk factors for dozens of common diseases.
The purpose of understanding the genetics of disease is to use that
information to create new means of diagnosing, treating and
preventing disease. deCODE is a wholly-owned subsidiary of Amgen
(NASDAQ:AMGN).
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