Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate.

Journal

Nature aging

ISSN: 2662-8465

Titre abrégé: Nat Aging

Pays: United States

ID NLM: 101773306

Informations de publication

Date de publication:
04 Jun 2024

Historique:

received: 29 06 2023

accepted: 08 05 2024

medline: 5 6 2024

pubmed: 5 6 2024

entrez: 4 6 2024

Statut: aheadofprint

Résumé

Clonal hematopoiesis of indeterminate potential (CHIP), whereby somatic mutations in hematopoietic stem cells confer a selective advantage and drive clonal expansion, not only correlates with age but also confers increased risk of morbidity and mortality. Here, we leverage genetically predicted traits to identify factors that determine CHIP clonal expansion rate. We used the passenger-approximated clonal expansion rate method to quantify the clonal expansion rate for 4,370 individuals in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) cohort and calculated polygenic risk scores for DNA methylation aging, inflammation-related measures and circulating protein levels. Clonal expansion rate was significantly associated with both genetically predicted and measured epigenetic clocks. No associations were identified with inflammation-related lab values or diseases and CHIP expansion rate overall. A proteome-wide search identified predicted circulating levels of myeloid zinc finger 1 and anti-Müllerian hormone as associated with an increased CHIP clonal expansion rate and tissue inhibitor of metalloproteinase 1 and glycine N-methyltransferase as associated with decreased CHIP clonal expansion rate. Together, our findings identify epigenetic and proteomic patterns associated with the rate of hematopoietic clonal expansion.

Identifiants

DOI: 10.1038/s43587-024-00647-7 PMID: 38834882

pubmed: 38834882

doi: 10.1038/s43587-024-00647-7

pii: 10.1038/s43587-024-00647-7

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Informations de copyright

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