دورية أكاديمية
Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease
| العنوان: | Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease |
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| المؤلفون: | Agha, G, Mendelson, M.M, Ward-Caviness, C.K, Joehanes, R, Huan, T, Gondalia, R, Salfati, E, 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. |
| المصدر: | Circulation, 140(8) |
| بيانات النشر: | NLM (Medline) |
| سنة النشر: | 2019 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | coronary heart disease, gene expression regulation, epigenetics, coronary artery disease, genomics |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/e2ke-q382Test; https://cdr.lib.unc.edu/downloads/5712mj23r?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/5712mj23rTest |
| DOI: | 10.17615/e2ke-q382 |
| الإتاحة: | https://doi.org/10.17615/e2ke-q382Test https://cdr.lib.unc.edu/downloads/5712mj23r?file=thumbnailTest https://cdr.lib.unc.edu/downloads/5712mj23rTest |
| رقم الانضمام: | edsbas.4003CAD |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/e2ke-q382 |
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