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Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.
Agha, Golareh; Mendelson, Michael M; Ward-Caviness, Cavin K; Joehanes, Roby; Huan, TianXiao; Gondalia, Rahul; Salfati, Elias; Brody, Jennifer A; Fiorito, Giovanni; Bressler, Jan; Chen, Brian H; Ligthart, Symen; Guarrera, Simonetta; Colicino, Elena; Just, Allan C; Wahl, Simone; Gieger, Christian; Vandiver, Amy R; Tanaka, Toshiko; Hernandez, Dena G; Pilling, Luke C; Singleton, Andrew B; Sacerdote, Carlotta; Krogh, Vittorio; Panico, Salvatore; Tumino, Rosario; Li, Yun; Zhang, Guosheng; Stewart, James D; Floyd, James S; Wiggins, Kerri L; Rotter, Jerome I; Multhaup, Michael; Bakulski, Kelly; Horvath, Steven; Tsao, Philip S; Absher, Devin M; Vokonas, Pantel; Hirschhorn, Joel; Fallin, M Daniele; Liu, Chunyu; Bandinelli, Stefania; Boerwinkle, Eric; Dehghan, Abbas; Schwartz, Joel D; Psaty, Bruce M; Feinberg, Andrew P; Hou, Lifang; Ferrucci, Luigi; Sotoodehnia, Nona.
Afiliação
  • Agha G; Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York (G.A., A.A.B.).
  • Mendelson MM; Population Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (M.M.M., D.L., R.J.).
  • Ward-Caviness CK; Framingham Heart Study, MA (M.M.M., D.L.).
  • Joehanes R; Department of Cardiology, Boston Children's Hospital, MA (M.M.M.).
  • Huan T; National Health and Environmental Effects Research Laboratory, Environmental Public Health Division, Chapel Hill, NC (C.K.W.C.).
  • Gondalia R; Institute of Epidemiology II, Helmholtz Institute, Ingolstaedter Landstrasse 1, Neuherberg, Germany (C.K.W.C.).
  • Salfati E; Population Sciences Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD (M.M.M., D.L., R.J.).
  • Brody JA; Hebrew SeniorLife, Harvard Medical School, Boston, MA (R.J.).
  • Fiorito G; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD (T.X.H.).
  • Bressler J; Department of Epidemiology (R.G.), University of North Carolina, Chapel Hill.
  • Chen BH; Department of Medicine, Stanford University School of Medicine, CA (E.S., P.S.T.).
  • Ligthart S; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
  • Guarrera S; Italian Institute for Genomic Medicine (IIGM/HuGeF) and Department of Medical Sciences, University of Turin, Italy (G.F., S.G., G.M.).
  • Colicino E; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston (J.B.).
  • Just AC; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD (B.H.C., T.T.).
  • Wahl S; Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands (S.L.).
  • Gieger C; Italian Institute for Genomic Medicine (IIGM/HuGeF) and Department of Medical Sciences, University of Turin, Italy (G.F., S.G., G.M.).
  • Vandiver AR; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY (E.C., A.C.J.).
  • Tanaka T; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY (E.C., A.C.J.).
  • Hernandez DG; Research Unit Molecualr Epidemiology, Helmholtz Zentrum München, Germany (S.W., C.G.).
  • Pilling LC; Research Unit Molecualr Epidemiology, Helmholtz Zentrum München, Germany (S.W., C.G.).
  • Singleton AB; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD (A.R.V., M.M.).
  • Sacerdote C; Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD (B.H.C., T.T.).
  • Krogh V; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD (D.G.H., A.B.S.).
  • Panico S; Epidemiology and Public Health Group, University of Exeter Medical School, United Kingdom (L.C.P.).
  • Tumino R; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD (D.G.H., A.B.S.).
  • Li Y; Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy (C.S.).
  • Zhang G; Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (V.K.).
  • Stewart JD; Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy (S.P.).
  • Floyd JS; Cancer Registry And Histopathology Department, Civic- M.P. Arezzo2 Hospital, Asp Ragusa, Italy (R.T.).
  • Wiggins KL; Department of Genetics, Department of Biostatistics, Department of Computer Science (Y.L.), University of North Carolina, Chapel Hill.
  • Rotter JI; Curriculum in Bioinformatics and Computational Biology, Department of Genetics, and Department of Statistics (G.Z.), University of North Carolina, Chapel Hill.
  • Multhaup M; Carolina Population Center and Department of Epidemiology (J.D.S.), University of North Carolina, Chapel Hill.
  • Bakulski K; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
  • Horvath S; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.A.B., J.S.F., K.L.W.).
  • Tsao PS; The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA (J.I.R.).
  • Absher DM; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD (A.R.V., M.M.).
  • Vokonas P; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor (K.B.).
  • Hirschhorn J; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles (S.H.).
  • Fallin MD; Department of Medicine, Stanford University School of Medicine, CA (E.S., P.S.T.).
  • Liu C; HudsonAlpha institute of Biotechnology, Huntsville, AL (D.M.A.).
  • Bandinelli S; VA Normative Aging Study, VA Boston Healthcare System, Department of Medicine, Boston University School of Medicine, MA (P.V.).
  • Boerwinkle E; Department of Medicine, Division of Endocrinology, Boston Children's Hospital, MA (J.H.).
  • Dehghan A; Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA (J.H.).
  • Schwartz JD; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (M.D.F.).
  • Psaty BM; Department of Biostatistics, Boston University School of Public Health, MA (C.L.).
  • Feinberg AP; Azienda Sanitaria, USL Centro Firenze, Italy (S.B.).
  • Hou L; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston (E.B.).
  • Ferrucci L; Human Genome Sequencing Center, Baylor College of Medicine, TX (E.B.).
  • Sotoodehnia N; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment & Health, School of 346 Public Health, Imperial College London, United Kingdom (A.D.).
Circulation ; 140(8): 645-657, 2019 08 20.
Article em En | MEDLINE | ID: mdl-31424985
ABSTRACT

BACKGROUND:

DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

METHODS:

Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

RESULTS:

Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.

CONCLUSION:

Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Doença das Coronárias / Leucócitos / Infarto do Miocárdio Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: America do norte / Europa Idioma: En Revista: Circulation Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ilhas de CpG / Metilação de DNA / Doença das Coronárias / Leucócitos / Infarto do Miocárdio Tipo de estudo: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Aged / Female / Humans / Male / Middle aged País/Região como assunto: America do norte / Europa Idioma: En Revista: Circulation Ano de publicação: 2019 Tipo de documento: Article