@article {9181, title = {{Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease}, journal = {Nat Commun}, volume = {13}, year = {2022}, month = {Sep}, pages = {5350}, 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. M. and Nguyen, N. Q. H. and Yu, B. and Brody, J. A. and Pampana, A. and Nakao, T. and Fornage, M. and Bressler, J. and Sotoodehnia, N. and Weinstock, J. S. and Honigberg, M. C. and Nachun, D. and Bhattacharya, R. and Griffin, G. K. and Chander, V. and Gibbs, R. A. and Rotter, J. I. and Liu, C. and Baccarelli, A. A. and Chasman, D. I. and Whitsel, E. A. and Kiel, D. P. and Murabito, J. M. and Boerwinkle, E. and Ebert, B. L. and Jaiswal, S. and Floyd, J. S. and Bick, A. G. and Ballantyne, C. M. and Psaty, B. M. and Natarajan, P. and Conneely, K. N.} }