Details

Autor(en) / Beteiligte

• 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
• Matullo, Giuseppe
• Peters, Annette
• Fornage, Myriam
• Assimes, Themistocles L
• Whitsel, Eric A
• Levy, Daniel
• Baccarelli, Andrea A

Titel

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

Ist Teil von

• Circulation (New York, N.Y.), 2019-08, Vol.140 (8), p.645-657

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2019

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.