Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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
Аннотация
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.