biostudies-literatureWard-Caviness CKNCATS NIH HHSNIDDK NIH HHSNIA NIH HHSNHLBI NIH HHSMedical Research CouncilDutch Research Council (NWO)Biotechnology and Biological Sciences Research Council1842-1850https://www.ebi.ac.uk/biostudies/studies/S-EPMC6202911biostudies-literatureUnknown132(17)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 = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) 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 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.BloodDNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.PMC6202911N01 HC085083U10 HL054481N01 HC085082N01 HC085081RC1 HL100185U01 HL054464N01 HC085086UL1 TR001881U01 HL080295R01 HL111089N01 HC085080184.021.007N01 HC025195R01 HL059367U01 HL120393R01 AG023629HHSN268201200036CR01 HL119443U01 HL054481U10 HL054464R01 HL087652U01 HL054457BB/F019394/1G0700704BR01 AG055406R01 HL134894R01 HL133221R01 HL120393R01 HL116747MR/K026992/1HHSN268200800007CK08 HL116640N01 HC055222R01 HL092111U10 HL054457R01 HL103612P30 DK063491N01 HC085079R01 HL105756U01 HL130114Psaty BMPeters AKardia SLRFranco-Cereceda AUitterlinden AGGuo XJohnson ADFranco OHWard-Caviness CKBoerwinkle EVan Meurs JBJProkisch HMorrison ACDeary IJGagnon FWiggins KLDehghan AGieger CSotoodenia NWillemsen GMorange PEBjorck HMBrody JALevy DTruong VPankow JSMcKnight BWare EBGermain MDu LTregouet DAEriksson PWaldenberger MHuffman JEZhao Wde Geus EJCvan Dongen JSmith NLTang WSmith JAGhanbari MWolf PKoenig WO'Donnell CJBoomsma DIRoetker NSEverett KWells PSJhun MAStarr JMLiu CHill WDde Vries PSLigthart LfalseDNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.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 = .01) and plasminogen activator inhibitor 1 (PAI-1; 0.13 U/mL/y; 95% confidence interval, 0.07-0.20; P = 6.6 × 10-5) 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 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.2018-01-01T00:00:00Z2018 Oct2026-05-06T00:17:34.011Z2019-11-05T08:04:16ZS-EPMC62029113004209810.1182/blood-2018-02-831347