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

TitleDNA methylation age is associated with an altered hemostatic profile in a multi-ethnic meta-analysis.
Publication TypeJournal Article
Year of Publication2018
AuthorsWard-Caviness, CK, Huffman, JE, Evertt, 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, Boomsa, 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
JournalBlood
Date Published2018 Jul 24
ISSN1528-0020
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 used European and African-ancestry participants who were meta-analyzed separately and combined via a random effects meta-analysis. All other measures only included participants of European-ancestry. We found that 1-year higher extrinsic epigenetic age as compared to chronological age was associated with higher fibrinogen (0.004 g/L per year; 95% CI: 0.001, 0.007; P = 0.01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL per year; 95% CI: 0.07, 0.20; P = 6.6x10-5) 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 three 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 pro-coagulation hemostatic profile, and that epigenetic aging may regulate hemostasis in part via gene transcription.

DOI10.1182/blood-2018-02-831347
Alternate JournalBlood
PubMed ID30042098