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

TitleDNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.
Publication TypeJournal Article
Year of Publication2018
AuthorsWard-Caviness, CK, Huffman, JE, Everett, K, Germain, M, van Dongen, J, W Hill, D, Jhun, MA, Brody, JA, Ghanbari, M, Du, L, Roetker, NS, de Vries, PS, Waldenberger, M, Gieger, C, Wolf, P, Prokisch, H, Koenig, W, O'Donnell, CJ, Levy, D, Liu, C, Truong, V, Wells, PS, Trégouët, D-A, Tang, W, Morrison, AC, Boerwinkle, E, Wiggins, KL, McKnight, B, Guo, X, Psaty, BM, Sotoodenia, N, Boomsma, DI, Willemsen, G, Ligthart, L, Deary, IJ, Zhao, W, Ware, EB, Kardia, SLR, van Meurs, JBJ, Uitterlinden, AG, Franco, OH, Eriksson, P, Franco-Cereceda, A, Pankow, JS, Johnson, AD, Gagnon, F, Morange, P-E, de Geus, EJC, Starr, JM, Smith, JA, Dehghan, A, Björck, HM, Smith, NL, Peters, A
Date Published2018 10 25
KeywordsAging, DNA Methylation, Epigenesis, Genetic, Hemostasis, Humans

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; = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; = 6.6 10) 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 () and the 3 fibrinogen subunit-encoding genes (, , and ) in both peripheral blood and aorta intima-media samples. We observed associations between accelerated epigenetic aging and transcription of 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.

Alternate JournalBlood
PubMed ID30042098
PubMed Central IDPMC6202911
Grant ListR01 HL059367 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
R01 HL133221 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
R01 HL134894 / HL / NHLBI NIH HHS / United States