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Genetics of smoking and risk of clonal hematopoiesis

Levin, Michael G. ; Nakao, Tetsushi ; Zekavat, Seyedeh M. ; Koyama, Satoshi LU orcid ; Bick, Alexander G. ; Niroula, Abhishek LU ; Ebert, Benjamin ; Damrauer, Scott M. and Natarajan, Pradeep (2022) In Scientific Reports 12(1).
Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) represent two forms of clonal hematopoiesis where clones bearing expanded somatic mutations have been linked to both oncologic and non-oncologic clinical outcomes including atherosclerosis and all-cause mortality. Epidemiologic studies have highlighted smoking as an important driver of somatic mutations across multiple tissues. However, establishing the causal role of smoking in clonal hematopoiesis has been limited by observational study designs, which may suffer from confounding and reverse-causality. We performed two complementary analyses to investigate the role of smoking in mCAs and CHIP. First, using an observational study design... (More)

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) represent two forms of clonal hematopoiesis where clones bearing expanded somatic mutations have been linked to both oncologic and non-oncologic clinical outcomes including atherosclerosis and all-cause mortality. Epidemiologic studies have highlighted smoking as an important driver of somatic mutations across multiple tissues. However, establishing the causal role of smoking in clonal hematopoiesis has been limited by observational study designs, which may suffer from confounding and reverse-causality. We performed two complementary analyses to investigate the role of smoking in mCAs and CHIP. First, using an observational study design among UK Biobank participants, we confirmed strong associations between smoking and mCAs. Second, using two-sample Mendelian randomization, smoking was strongly associated with mCA but not with CHIP. Overall, these results support a causal association between smoking and mCAs and suggest smoking may variably shape the fitness of clones bearing somatic mutations.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
12
issue
1
article number
7248
publisher
Nature Publishing Group
external identifiers
  • scopus:85129423781
  • pmid:35508625
ISSN
2045-2322
DOI
10.1038/s41598-022-09604-z
language
English
LU publication?
yes
id
0584604a-169d-41fd-bce0-ff0586d4a6d7
date added to LUP
2022-07-06 15:03:32
date last changed
2024-02-17 19:47:34
@article{0584604a-169d-41fd-bce0-ff0586d4a6d7,
  abstract     = {{<p>Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) represent two forms of clonal hematopoiesis where clones bearing expanded somatic mutations have been linked to both oncologic and non-oncologic clinical outcomes including atherosclerosis and all-cause mortality. Epidemiologic studies have highlighted smoking as an important driver of somatic mutations across multiple tissues. However, establishing the causal role of smoking in clonal hematopoiesis has been limited by observational study designs, which may suffer from confounding and reverse-causality. We performed two complementary analyses to investigate the role of smoking in mCAs and CHIP. First, using an observational study design among UK Biobank participants, we confirmed strong associations between smoking and mCAs. Second, using two-sample Mendelian randomization, smoking was strongly associated with mCA but not with CHIP. Overall, these results support a causal association between smoking and mCAs and suggest smoking may variably shape the fitness of clones bearing somatic mutations.</p>}},
  author       = {{Levin, Michael G. and Nakao, Tetsushi and Zekavat, Seyedeh M. and Koyama, Satoshi and Bick, Alexander G. and Niroula, Abhishek and Ebert, Benjamin and Damrauer, Scott M. and Natarajan, Pradeep}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Genetics of smoking and risk of clonal hematopoiesis}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-09604-z}},
  doi          = {{10.1038/s41598-022-09604-z}},
  volume       = {{12}},
  year         = {{2022}},
}