Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease

M d Mesbah Uddin, Ngoc Quynh H. Nguyen, Bing Yu, Jennifer A. Brody, Akhil Pampana, Tetsushi Nakao, Myriam Fornage, Jan Bressler, Nona Sotoodehnia, Joshua S. Weinstock, Michael C. Honigberg, Daniel Nachun, Romit Bhattacharya, Gabriel K. Griffin, Varuna Chander, Richard A. Gibbs, Jerome I. Rotter, Chunyu Liu, Andrea A. Baccarelli, Daniel I. Chasman, Eric A. Whitsel, Douglas P. Kiel, Joanne M. Murabito, Eric Boerwinkle, Benjamin L. Ebert, Siddhartha Jaiswal, James S. Floyd, Alexander G. Bick, Christie M. Ballantyne, Bruce M. Psaty, Pradeep Natarajan () and Karen N. Conneely ()
Additional contact information
M d 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
Akhil Pampana: Broad Institute of Harvard and MIT
Tetsushi Nakao: Broad Institute of Harvard and MIT
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
Joshua S. Weinstock: University of Michigan School of Public Health
Michael C. Honigberg: Broad Institute of Harvard and MIT
Daniel Nachun: Stanford University School of Medicine
Romit Bhattacharya: Broad Institute of Harvard and MIT
Gabriel K. Griffin: Dana-Farber Cancer Institute
Varuna Chander: Baylor College of Medicine
Richard A. Gibbs: Baylor College of Medicine
Jerome I. Rotter: The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Chunyu Liu: School of Public Health, Boston University
Andrea A. Baccarelli: Columbia University
Daniel I. Chasman: Harvard Medical School
Eric A. Whitsel: University of North Carolina
Douglas P. Kiel: Harvard Medical School
Joanne M. Murabito: Boston University and NHLBI/NIH
Eric Boerwinkle: The University of Texas Health Science Center at Houston
Benjamin L. Ebert: Dana-Farber Cancer Institute
Siddhartha Jaiswal: Stanford University School of Medicine
James S. Floyd: University of Washington
Alexander G. Bick: Vanderbilt University Medical Center
Christie M. Ballantyne: Baylor College of Medicine
Bruce M. Psaty: University of Washington
Pradeep Natarajan: Broad Institute of Harvard and MIT
Karen N. Conneely: Emory University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-33093-3 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:13:y:2022:i:1:d:10.1038_s41467-022-33093-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-33093-3

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 ().