{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ward-Caviness CK"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NIA NIH HHS","NHLBI NIH HHS","Medical Research Council","Dutch Research Council (NWO)","Biotechnology and Biological Sciences Research Council"],"pagination":["1842-1850"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6202911"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["132(17)"],"pubmed_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 = .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."],"journal":["Blood"],"pubmed_title":["DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis."],"pmcid":["PMC6202911"],"funding_grant_id":["N01 HC085083","U10 HL054481","N01 HC085082","N01 HC085081","RC1 HL100185","U01 HL054464","N01 HC085086","UL1 TR001881","U01 HL080295","R01 HL111089","N01 HC085080","184.021.007","N01 HC025195","R01 HL059367","U01 HL120393","R01 AG023629","HHSN268201200036C","R01 HL119443","U01 HL054481","U10 HL054464","R01 HL087652","U01 HL054457","BB/F019394/1","G0700704B","R01 AG055406","R01 HL134894","R01 HL133221","R01 HL120393","R01 HL116747","MR/K026992/1","HHSN268200800007C","K08 HL116640","N01 HC055222","R01 HL092111","U10 HL054457","R01 HL103612","P30 DK063491","N01 HC085079","R01 HL105756","U01 HL130114"],"pubmed_authors":["Psaty BM","Peters A","Kardia SLR","Franco-Cereceda A","Uitterlinden AG","Guo X","Johnson AD","Franco OH","Ward-Caviness CK","Boerwinkle E","Van Meurs JBJ","Prokisch H","Morrison AC","Deary IJ","Gagnon F","Wiggins KL","Dehghan A","Gieger C","Sotoodenia N","Willemsen G","Morange PE","Bjorck HM","Brody JA","Levy D","Truong V","Pankow JS","McKnight B","Ware EB","Germain M","Du L","Tregouet DA","Eriksson P","Waldenberger M","Huffman JE","Zhao W","de Geus EJC","van Dongen J","Smith NL","Tang W","Smith JA","Ghanbari M","Wolf P","Koenig W","O'Donnell CJ","Boomsma DI","Roetker NS","Everett K","Wells PS","Jhun MA","Starr JM","Liu C","Hill WD","de Vries PS","Ligthart L"],"additional_accession":[]},"is_claimable":false,"name":"DNA methylation age is associated with an altered hemostatic profile in a multiethnic meta-analysis.","description":"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.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2026-05-06T00:17:34.011Z","creation":"2019-11-05T08:04:16Z"},"accession":"S-EPMC6202911","cross_references":{"pubmed":["30042098"],"doi":["10.1182/blood-2018-02-831347"]}}