Epigenome-wide DNA methylation association study of CHIP provides insight into perturbed gene regulation
Sara Kirmani,
Tianxiao Huan (),
Joseph C. Amburg,
Roby Joehanes,
Md Mesbah Uddin,
Ngoc Quynh H. Nguyen,
Bing Yu,
Jennifer A. Brody,
Myriam Fornage,
Jan Bressler,
Nona Sotoodehnia,
David A. Ong,
Fabio Puddu,
James S. Floyd,
Christie M. Ballantyne,
Bruce M. Psaty,
Laura M. Raffield,
Pradeep Natarajan,
Karen N. Conneely,
Joshua S. Weinstock,
April P. Carson,
Leslie A. Lange,
Kendra Ferrier,
Nancy L. Heard-Costa,
Joanne Murabito,
Alexander G. Bick () and
Daniel Levy ()
Additional contact information
Sara Kirmani: Framingham Heart Study
Tianxiao Huan: Framingham Heart Study
Joseph C. Amburg: Vanderbilt University Medical Center
Roby Joehanes: Framingham Heart Study
Md Mesbah Uddin: Broad Institute of Harvard and MIT
Ngoc Quynh H. Nguyen: The University of Texas Health Science Center at Houston
Bing Yu: The University of Texas Health Science Center at Houston
Jennifer A. Brody: University of Washington
Myriam Fornage: University of Texas Health Science Center at Houston
Jan Bressler: The University of Texas Health Science Center at Houston
Nona Sotoodehnia: University of Washington
David A. Ong: Vanderbilt University Medical Center
Fabio Puddu: Chesterford Research Park
James S. Floyd: University of Washington
Christie M. Ballantyne: Baylor College of Medicine
Bruce M. Psaty: University of Washington
Laura M. Raffield: University of North Carolina
Pradeep Natarajan: Broad Institute of Harvard and MIT
Karen N. Conneely: Emory University School of Medicine
Joshua S. Weinstock: Emory University School of Medicine
April P. Carson: University of Mississippi Medical Center
Leslie A. Lange: University of Colorado at Denver
Kendra Ferrier: University of Colorado at Denver
Nancy L. Heard-Costa: Framingham Heart Study
Joanne Murabito: Framingham Heart Study
Alexander G. Bick: Vanderbilt University Medical Center
Daniel Levy: Framingham Heart Study
Nature Communications, 2025, vol. 16, issue 1, 1-14
Abstract:
Abstract With age, hematopoietic stem cells can acquire somatic mutations in leukemogenic genes that confer a proliferative advantage in a phenomenon termed CHIP. How these mutations result in increased risk for numerous age-related diseases remains poorly understood. We conduct a multiracial meta-analysis of EWAS of CHIP in the Framingham Heart Study, Jackson Heart Study, Cardiovascular Health Study, and Atherosclerosis Risk in Communities cohorts (N = 8196) to elucidate the molecular mechanisms underlying CHIP and illuminate how these changes influence cardiovascular disease risk. We functionally validate the EWAS findings using human hematopoietic stem cell models of CHIP. We then use expression quantitative trait methylation analysis to identify transcriptomic changes associated with CHIP-associated CpGs. Causal inference analyses reveal 261 CHIP-associated CpGs associated with cardiovascular traits and all-cause mortality (FDR adjusted p-value
Date: 2025
References: Add references at CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/s41467-025-59333-w Abstract (text/html)
Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.
Export reference: BibTeX
RIS (EndNote, ProCite, RefMan)
HTML/Text
Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59333-w
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-025-59333-w
Access Statistics for this article
Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie
More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().