Genetics of smoking and risk of clonal hematopoiesis.
Sci Rep
; 12(1): 7248, 2022 05 04.
Article
en En
| MEDLINE
| ID: mdl-35508625
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 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Aterosclerosis
/
Hematopoyesis Clonal
Tipo de estudio:
Clinical_trials
/
Etiology_studies
/
Observational_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article