Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease. Uddin, M D M., Nguyen, N. Q. H, Yu, B., Brody, J. A, Pampana, A., Nakao, T., Fornage, M., Bressler, J., Sotoodehnia, N., Weinstock, J. S, Honigberg, M. C, Nachun, D., Bhattacharya, R., Griffin, G. K, Chander, V., Gibbs, R. A, Rotter, J. I, Liu, C., Baccarelli, A. A, Chasman, D. I, Whitsel, E. A, Kiel, D. P, Murabito, J. M, Boerwinkle, E., Ebert, B. L, Jaiswal, S., Floyd, J. S, Bick, A. G, Ballantyne, C. M, Psaty, B. M, Natarajan, P., & Conneely, K. N Nat Commun, 13(1):5350, Sep, 2022. ![Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{Uddin:2022aa,
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.},
author = {Uddin, M D Mesbah and Nguyen, Ngoc Quynh H and Yu, Bing and Brody, Jennifer A and Pampana, Akhil and Nakao, Tetsushi and Fornage, Myriam and Bressler, Jan and Sotoodehnia, Nona and Weinstock, Joshua S and Honigberg, Michael C and Nachun, Daniel and Bhattacharya, Romit and Griffin, Gabriel K and Chander, Varuna and Gibbs, Richard A and Rotter, Jerome I and Liu, Chunyu and Baccarelli, Andrea A and Chasman, Daniel I and Whitsel, Eric A and Kiel, Douglas P and Murabito, Joanne M and Boerwinkle, Eric and Ebert, Benjamin L and Jaiswal, Siddhartha and Floyd, James S and Bick, Alexander G and Ballantyne, Christie M and Psaty, Bruce M and Natarajan, Pradeep and Conneely, Karen N},
date-added = {2024-05-19 20:58:22 -0400},
date-modified = {2024-05-19 20:58:22 -0400},
doi = {10.1038/s41467-022-33093-3},
journal = {Nat Commun},
journal-full = {Nature communications},
mesh = {Clonal Hematopoiesis; Coronary Artery Disease; DNA Methylation; Hematopoiesis; Hematopoietic Stem Cells; Humans},
month = {Sep},
number = {1},
pages = {5350},
pmc = {PMC9468335},
pmid = {36097025},
url = {https://pubmed.ncbi.nlm.nih.gov/36097025/},
pst = {epublish},
title = {Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease},
volume = {13},
year = {2022},
bdsk-url-1 = {https://doi.org/10.1038/s41467-022-33093-3}}
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