@article {9983,
	title = {Epigenome-wide DNA methylation association study of CHIP provides insight into perturbed gene regulation.},
	journal = {Nat Commun},
	volume = {16},
	year = {2025},
	month = {2025 May 20},
	pages = {4678},
	abstract = {<p>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 < 0.05). Taken together, our study reports the epigenetic changes impacted by CHIP and their associations with age-related disease outcomes.</p>},
	keywords = {Aged, Atherosclerosis, Cardiovascular Diseases, CpG Islands, DNA Methylation, Epigenesis, Genetic, Epigenome, Female, Gene Expression Regulation, Genome-Wide Association Study, Hematopoietic Stem Cells, Humans, Male, Middle Aged},
	issn = {2041-1723},
	doi = {10.1038/s41467-025-59333-w},
	author = {Kirmani, Sara and Huan, Tianxiao and Van Amburg, Joseph C and Joehanes, Roby and Uddin, Md Mesbah and Nguyen, Ngoc Quynh H and Yu, Bing and Brody, Jennifer A and Fornage, Myriam and Bressler, Jan and Sotoodehnia, Nona and Ong, David A and Puddu, Fabio and Floyd, James S and Ballantyne, Christie M and Psaty, Bruce M and Raffield, Laura M and Natarajan, Pradeep and Conneely, Karen N and Weinstock, Joshua S and Carson, April P and Lange, Leslie A and Ferrier, Kendra and Heard-Costa, Nancy L and Murabito, Joanne and Bick, Alexander G and Levy, Daniel}
}
