PuSH - Publication Server of Helmholtz Zentrum München

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.
Additional Metrics?
Edit extra informations Login
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