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Agha, G.* ; Mendelson, M.M.* ; Ward-Caviness, C.K. ; Joehanes, R.* ; Huan, T.* ; Gondalia, R.* ; Salfati, E.L.* ; Brody, J.A.* ; Fiorito, G.* ; Bressler, J.* ; Chen, B.H.* ; Ligthart, S.* ; Guarrera, S.* ; Colicino, E.* ; Just, A.C.* ; Wahl, S. ; Gieger, C. ; Vandiver, A.R.* ; Tanaka, T.* ; Hernandez, D.G.* ; Pilling, L.C.* ; Singleton, A.B.* ; Sacerdote, C.* ; Krogh, V.* ; Panico, S.* ; Tumino, R.* ; Li, Y.* ; Zhang, G.* ; Stewart, J.D.* ; Floyd, J.S.* ; Wiggins, K.L.* ; Rotter, J.I.* ; Multhaup, M.* ; Bakulski, K.* ; Horvath, S.* ; Tsao, P.S.* ; Absher, D.M.* ; Vokonas, P.* ; Hirschhorn, J.* ; Fallin, M.D.* ; Liu, C.* ; Bandinelli, S.* ; Boerwinkle, E.* ; Dehghan, A.* ; Schwartz, J.D.* ; Psaty, B.M.* ; Feinberg, A.P.* ; Hou, L.* ; Ferrucci, L.* ; Sotoodehnia, N.* ; Matullo, G.* ; Peters, A. ; Fornage, M.* ; Assimes, T.L.* ; Whitsel, E.A.* ; Levy, D.* ; Baccarelli, A.A.*

Blood leukocyte DNA methylation predicts risk of future myocardial infarction and coronary heart disease: A longitudinal study of 11,461 participants from population-based cohorts.

Circulation 140, 645-657 (2019)
Publ. Version/Full Text Research data DOI
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Coronary Artery Disease ; Coronary Heart Disease ; Epigenetics ; Genomics ; Gene Expression Regulation; Genome-wide Association; Cardiovascular-disease; Biased Selection; Artery-disease; Metaanalysis; Hypomethylation; Insulin; Stroke; Genes; Model
ISSN (print) / ISBN 0009-7322
e-ISSN 1524-4539
Journal Circulation
Quellenangaben Volume: 140, Issue: 8, Pages: 645-657 Article Number: , Supplement: ,
Publisher Lippincott Williams & Wilkins
Publishing Place Two Commerce Sq, 2001 Market St, Philadelphia, Pa 19103 Usa
Reviewing status Peer reviewed