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Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. 2019
Golareh Agha, and
Michael M Mendelson, and
Cavin K Ward-Caviness, and
Roby Joehanes, and
TianXiao Huan, and
Rahul Gondalia, and
Elias Salfati, and
Jennifer A Brody, and
Giovanni Fiorito, and
Jan Bressler, and
Brian H Chen, and
Symen Ligthart, and
Simonetta Guarrera, and
Elena Colicino, and
Allan C Just, and
Simone Wahl, and
Christian Gieger, and
Amy R Vandiver, and
Toshiko Tanaka, and
Dena G Hernandez, and
Luke C Pilling, and
Andrew B Singleton, and
Carlotta Sacerdote, and
Vittorio Krogh, and
Salvatore Panico, and
Rosario Tumino, and
Yun Li, and
Guosheng Zhang, and
James D Stewart, and
James S Floyd, and
Kerri L Wiggins, and
Jerome I Rotter, and
Michael Multhaup, and
Kelly Bakulski, and
Steven Horvath, and
Philip S Tsao, and
Devin M Absher, and
Pantel Vokonas, and
Joel Hirschhorn, and
M Daniele Fallin, and
Chunyu Liu, and
Stefania Bandinelli, and
Eric Boerwinkle, and
Abbas Dehghan, and
Joel D Schwartz, and
Bruce M Psaty, and
Andrew P Feinberg, and
Lifang Hou, and
Luigi Ferrucci, and
Nona Sotoodehnia, and
Giuseppe Matullo, and
Annette Peters, and
Myriam Fornage, and
Themistocles L Assimes, and
Eric A Whitsel, and
Daniel Levy, and
Andrea A Baccarelli
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York (G.A., A.A.B.).
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. 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. 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. 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.
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Elias Salfati, and
Jennifer A Brody, and
Giovanni Fiorito, and
Jan Bressler, and
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Carlotta Sacerdote, and
Vittorio Krogh, and
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Rosario Tumino, and
Yun Li, and
Guosheng Zhang, and
James D Stewart, and
James S Floyd, and
Kerri L Wiggins, and
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Michael Multhaup, and
Kelly Bakulski, and
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Philip S Tsao, and
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TianXiao Huan, and
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Elias Salfati, and
Jennifer A Brody, and
Giovanni Fiorito, and
Jan Bressler, and
Brian H Chen, and
Symen Ligthart, and
Simonetta Guarrera, and
Elena Colicino, and
Allan C Just, and
Simone Wahl, and
Christian Gieger, and
Amy R Vandiver, and
Toshiko Tanaka, and
Dena G Hernandez, and
Luke C Pilling, and
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Carlotta Sacerdote, and
Vittorio Krogh, and
Salvatore Panico, and
Rosario Tumino, and
Yun Li, and
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James D Stewart, and
James S Floyd, and
Kerri L Wiggins, and
Jerome I Rotter, and
Michael Multhaup, and
Kelly Bakulski, and
Steven Horvath, and
Philip S Tsao, and
Devin M Absher, and
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Joel Hirschhorn, and
M Daniele Fallin, and
Chunyu Liu, and
Stefania Bandinelli, and
Eric Boerwinkle, and
Abbas Dehghan, and
Joel D Schwartz, and
Bruce M Psaty, and
Andrew P Feinberg, and
Lifang Hou, and
Luigi Ferrucci, and
Nona Sotoodehnia, and
Giuseppe Matullo, and
Annette Peters, and
Myriam Fornage, and
Themistocles L Assimes, and
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Daniel Levy, and
Andrea A Baccarelli
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Golareh Agha, and
Michael M Mendelson, and
Cavin K Ward-Caviness, and
Roby Joehanes, and
TianXiao Huan, and
Rahul Gondalia, and
Elias Salfati, and
Jennifer A Brody, and
Giovanni Fiorito, and
Jan Bressler, and
Brian H Chen, and
Symen Ligthart, and
Simonetta Guarrera, and
Elena Colicino, and
Allan C Just, and
Simone Wahl, and
Christian Gieger, and
Amy R Vandiver, and
Toshiko Tanaka, and
Dena G Hernandez, and
Luke C Pilling, and
Andrew B Singleton, and
Carlotta Sacerdote, and
Vittorio Krogh, and
Salvatore Panico, and
Rosario Tumino, and
Yun Li, and
Guosheng Zhang, and
James D Stewart, and
James S Floyd, and
Kerri L Wiggins, and
Jerome I Rotter, and
Michael Multhaup, and
Kelly Bakulski, and
Steven Horvath, and
Philip S Tsao, and
Devin M Absher, and
Pantel Vokonas, and
Joel Hirschhorn, and
M Daniele Fallin, and
Chunyu Liu, and
Stefania Bandinelli, and
Eric Boerwinkle, and
Abbas Dehghan, and
Joel D Schwartz, and
Bruce M Psaty, and
Andrew P Feinberg, and
Lifang Hou, and
Luigi Ferrucci, and
Nona Sotoodehnia, and
Giuseppe Matullo, and
Annette Peters, and
Myriam Fornage, and
Themistocles L Assimes, and
Eric A Whitsel, and
Daniel Levy, and
Andrea A Baccarelli
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Golareh Agha, and
Michael M Mendelson, and
Cavin K Ward-Caviness, and
Roby Joehanes, and
TianXiao Huan, and
Rahul Gondalia, and
Elias Salfati, and
Jennifer A Brody, and
Giovanni Fiorito, and
Jan Bressler, and
Brian H Chen, and
Symen Ligthart, and
Simonetta Guarrera, and
Elena Colicino, and
Allan C Just, and
Simone Wahl, and
Christian Gieger, and
Amy R Vandiver, and
Toshiko Tanaka, and
Dena G Hernandez, and
Luke C Pilling, and
Andrew B Singleton, and
Carlotta Sacerdote, and
Vittorio Krogh, and
Salvatore Panico, and
Rosario Tumino, and
Yun Li, and
Guosheng Zhang, and
James D Stewart, and
James S Floyd, and
Kerri L Wiggins, and
Jerome I Rotter, and
Michael Multhaup, and
Kelly Bakulski, and
Steven Horvath, and
Philip S Tsao, and
Devin M Absher, and
Pantel Vokonas, and
Joel Hirschhorn, and
M Daniele Fallin, and
Chunyu Liu, and
Stefania Bandinelli, and
Eric Boerwinkle, and
Abbas Dehghan, and
Joel D Schwartz, and
Bruce M Psaty, and
Andrew P Feinberg, and
Lifang Hou, and
Luigi Ferrucci, and
Nona Sotoodehnia, and
Giuseppe Matullo, and
Annette Peters, and
Myriam Fornage, and
Themistocles L Assimes, and
Eric A Whitsel, and
Daniel Levy, and
Andrea A Baccarelli
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