DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis

Ward-Caviness, C. K. and Huffman, J. E. and Everett, K. and Germain, M. and Van Dongen, J. and Hill, W. D. and Jhun, M. A. and Brody, J. A. and Ghanbari, M. and Du, L. and Roetker, N. S. and De Vries, P. S. and Waldenberger, M. and Gieger, C. and Wolf, P. and Prokisch, H. and Koenig, W. and O’Donnell, C. J. and Levy, D. and Liu, C. and Truong, V. and Wells, P. S. and Trégouët, D. A. and Tang, W. and Morrison, A. C. and Boerwinkle, E. and Wiggins, K. L. and McKnight, B. and Guo, X. and Psaty, B. M. and Sotoodenia, N. and Boomsma, D. I. and Willemsen, G. and Ligthart, L. and Deary, I. J. and Zhao, W. and Ware, E. B. and Kardia, S. L. R. and Van Meurs, J. B. J. and Uitterlinden, A. G. and Franco, O. H. and Eriksson, P. and Franco-Cereceda, A. and Pankow, J. S. and Johnson, A. D. and Gagnon, F. and Morange, P. E. and De Geus, E. J. C. and Starr, J. M. and Smith, J. A. and Dehghan, A. and Björck, H. M. and Smith, N. L. and Peters, A. (2018) DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis. Blood, 132 (17). pp. 1842-1850.

[img] Text
DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis .pdf

Download (904kB)

Abstract

Many hemostatic factors are associated with age and age-related diseases; however, much remains unknown about the biological mechanisms linking aging and hemostatic factors. DNA methylation is a novel means by which to assess epigenetic aging, which is a measure of age and the aging processes as determined by altered epigenetic states. We used a meta-analysis approach to examine the association between measures of epigenetic aging and hemostatic factors, as well as a clotting time measure. For fibrinogen, we performed European and African ancestry–specific meta-analyses which were then combined via a random effects meta-analysis. For all other measures we could not estimate ancestry-specific effects and used a single fixed effects meta-analysis. We found that 1-year higher extrinsic epigenetic age as compared with chronological age was associated with higher fibrinogen (0.004 g/L/y; 95 confidence interval, 0.001-0.007; P 5 .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95 confidence interval, 0.07-0.20; P 5 6.6 3 1025) concentrations, as well as lower activated partial thromboplastin time, a measure of clotting time. We replicated PAI-1 associations using an independent cohort. To further elucidate potential functional mechanisms, we associated epigenetic aging with expression levels of the PAI-1 protein encoding gene (SERPINE1) and the 3 fibrinogen subunit-encoding genes (FGA, FGG, and FGB) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of FGG in both tissues. Collectively, our results indicate that accelerated epigenetic aging is associated with a procoagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription. Copyright © 2011 by The American Society of Hematology; all rights reserved.

Item Type: Article
Additional Information: Cited By :3 Export Date: 16 February 2020 CODEN: BLOOA Correspondence Address: Ward-Caviness, C.K.; Institute of Epidemiology II, Helmholtz Center of MunichGermany; email: ward-caviness.cavin@epa.gov
Uncontrolled Keywords: biological marker fibrinogen plasminogen activator inhibitor 1 activated partial thromboplastin time age aging aortic intima Article blood clotting time DNA methylation epigenetics gene expression genetic transcription hemostasis human priority journal genetic epigenesis meta analysis pathology physiology Epigenesis, Genetic Humans
Subjects: QU Biochemistry
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 27 Apr 2020 07:07
Last Modified: 27 Apr 2020 07:07
URI: http://eprints.mums.ac.ir/id/eprint/17574

Actions (login required)

View Item View Item