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

被引：17

作者：

Ward-Caviness, Cavin K. ^{[1
,2
]}

Huffman, Jennifer E. ^{[3
,4
,5
]}

Everett, Karl ^{[6
]}

Germain, Marine ^{[7
,8
]}

van Dongen, Jenny ^{[9
]}

Hill, W. David ^{[10
,11
]}

Jhun, Min A. ^{[12
]}

Brody, Jennifer A. ^{[13
,14
]}

Ghanbari, Mohsen ^{[15
,16
]}

Du, Lei ^{[17
]}

Roetker, Nicholas S. ^{[18
]}

de Vries, Paul S. ^{[19
]}

Waldenberger, Melanie ^{[1
,20
]}

Gieger, Christian ^{[20
]}

Wolf, Petra ^{[21
]}

Prokisch, Holger ^{[21
,22
]}

Koenig, Wolfgang ^{[23
,24
,25
]}

O'Donnell, Christopher J. ^{[4
,26
]}

Levy, Daniel ^{[3
,4
]}

Liu, Chunyu ^{[3
,4
]}

Vinh Truong ^{[6
]}

Wells, Philip S. ^{[27
,28
]}

Tregouet, David-Alexandre ^{[7
,8
]}

Tang, Weihong ^{[18
]}

Morrison, Alanna C. ^{[19
]}

Boerwinkle, Eric ^{[19
,29
]}

Wiggins, Kerri L. ^{[13
,14
]}

McKnight, Barbara ^{[13
,30
]}

Guo, Xiuqing ^{[31
]}

Psaty, Bruce M. ^{[13
,14
,32
,33
,34
]}

Sotoodenia, Nona ^{[13
,14
,35
]}

Boomsma, Dorret I. ^{[9
]}

Willemsen, Gonneke ^{[9
]}

Ligthart, Lannie ^{[9
]}

Deary, Ian J. ^{[10
,11
]}

Zhao, Wei ^{[12
]}

Ware, Erin B. ^{[36
]}

Kardia, Sharon L. R. ^{[12
]}

Van Meurs, Joyce B. J. ^{[37
]}

Uitterlinden, Andre G. ^{[37
]}

Franco, Oscar H. ^{[15
]}

Eriksson, Per ^{[17
]}

Franco-Cereceda, Anders ^{[38
]}

Pankow, James S. ^{[18
]}

Johnson, Andrew D. ^{[3
,4
]}

Gagnon, France ^{[6
]}

Morange, Pierre-Emmanuel ^{[39
,40
]}

de Geus, Eco J. C. ^{[9
,41
]}

Starr, John M. ^{[10
,42
]}

Smith, Jennifer A. ^{[12
,36
]}

机构：

[1] Helmholtz Ctr Munich, Inst Epidemiol 2, Neuherberg, Germany

[2] US EPA, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, 104 Mason Farm Rd, Chapel Hill, NC 27517 USA

[3] NHLBI, Populat Sci Branch, NIH, Framingham, MA USA

[4] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[5] Boston VA Healthcare Syst, Ctr Populat Genom, Jamaica Plain, MA USA

[6] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada

[7] UPMC Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1166, Paris, France

[8] ICAN Inst Cardiometab & Nutr, Paris, France

[9] Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands

[10] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[11] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[12] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA

[13] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[14] Univ Washington, Dept Med, Seattle, WA USA

[15] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[16] Mashhad Univ Med Sci, Dept Genet, Sch Med, Mashhad, Iran

[17] Karolinska Inst, Cardiovasc Med Unit, Ctr Mol Med, Dept Med,Karolinska Univ Hosp Solna, Stockholm, Sweden

[18] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[19] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX 77030 USA

[20] Helmholtz Ctr Munich, Res Unit Mol Epidemiol, Neuherberg, Germany

[21] Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany

[22] Tech Univ Munich, Inst Humangenet, Munich, Germany

[23] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany

[24] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany

[25] Munich Heart Alliance, German Ctr Cardiovasc Res, Munich, Germany

[26] Boston VA Healthcare Syst, Cardiol Sect Adm, West Roxbury, MA USA

[27] Univ Ottawa, Dept Med, Ottawa, ON, Canada

[28] Ottawa Hosp, Res Inst, Ottawa, ON, Canada

[29] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[30] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[31] Harbor UCLA Med Ctr, Dept Pediat, LABioMed, Torrance, CA USA

[32] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[33] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[34] Kaiser Permanente Washington, Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA

[35] Univ Washington, Div Cardiol, Seattle, WA 98195 USA

[36] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA

[37] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[38] Karolinska Inst, Cardiothorac Surg Unit, Dept Mol Med & Surg, Stockholm, Sweden

[39] La Timone Hosp, Hematol Lab, Marseille, France

[40] Aix Marseille Univ, INSERM, UMR S 1062, Nutr Obes & Risk Thrombosis,Ctr CardioVasc & Nutr, Marseille, France

[41] Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth, Amsterdam, Netherlands

[42] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland

[43] Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Dept Vet Affairs, Seattle, WA USA

来源：

BLOOD | 2018年 / 132卷 / 17期

基金：

英国医学研究理事会; 美国国家卫生研究院; 英国生物技术与生命科学研究理事会; 瑞典研究理事会; 加拿大健康研究院;

关键词：

ACTIVATOR INHIBITOR-1 PAI-1; ALL-CAUSE MORTALITY; EPIGENETIC AGE; MYOCARDIAL-INFARCTION; TELOMERE LENGTH; PLASMA-FIBRINOGEN; FACTOR-VIII; DISEASE; BLOOD; RISK;

D O I：

10.1182/blood-2018-02-831347

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 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.

引用

页码：1842 / 1850

页数：9

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