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. Issue 8 (20th August 2019)

• Record Type: Journal Article
• Authors: 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.;
• Is Part Of: Circulation. Volume 140:Issue 8(2019)
• Publication Date: 2019-08-20
• Subjects: coronary artery disease -- coronary heart disease -- epigenetics -- genomics -- gene expression regulation; Blood -- Circulation -- Periodicals; Cardiovascular system -- Periodicals; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; 616.1
• DOI: 10.1161/CIRCULATIONAHA.118.039357
• Languages: English
• ISSNs: 0009-7322

Abstract

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. Abstract : Supplemental Digital Content is available in the text.