Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

G. Agha; M. M. Mendelson; C. K. Ward-Caviness; R. Joehanes; T. Huan; R. Gondalia; E. Salfati; J. A. Brody; G. Fiorito; J. Bressler; B. H. Chen; S. Ligthart; S. Guarrera; E. Colicino; A. C. Just; S. Wahl; C. Gieger; A. R. Vandiver; T. Tanaka; D. G. Hernandez; L. C. Pilling; A. B. Singleton; Carlotta SACERDOTE; V. Krogh; S. Panico; R. Tumino; Y. Li; G. Zhang; J. D. Stewart; J. S. Floyd; K. L. Wiggins; J. I. Rotter; M. Multhaup; K. Bakulski; S. Horvath; P. S. Tsao; D. M. Absher; P. Vokonas; J. Hirschhorn; M. D. Fallin; C. Liu; S. Bandinelli; E. Boerwinkle; A. Dehghan; J. D. Schwartz; B. M. Psaty; A. P. Feinberg; L. Hou; L. Ferrucci; N. Sotoodehnia; G. Matullo; A. Peters; M. Fornage; T. L. Assimes; E. A. Whitsel; D. Levy; A. A. Baccarelli

doi:10.1161/CIRCULATIONAHA.118.039357

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

G. Agha, M. M. Mendelson, C. K. Ward-Caviness, R. Joehanes, T. Huan, R. Gondalia, E. Salfati, J. A. Brody, G. Fiorito, J. Bressler, B. H. Chen, S. Ligthart, S. Guarrera, E. Colicino, A. C. Just, S. Wahl, C. Gieger, A. R. Vandiver, T. Tanaka, D. G. HernandezL. C. Pilling, A. B. Singleton, Carlotta SACERDOTE, V. Krogh, S. Panico, R. Tumino, Y. Li, G. Zhang, J. D. Stewart, J. S. Floyd, K. L. Wiggins, J. I. Rotter, M. Multhaup, K. Bakulski, S. Horvath, P. S. Tsao, D. M. Absher, P. Vokonas, J. Hirschhorn, M. D. Fallin, C. Liu, S. Bandinelli, E. Boerwinkle, A. Dehghan, J. D. Schwartz, B. M. Psaty, A. P. Feinberg, L. Hou, L. Ferrucci, N. Sotoodehnia, G. Matullo, A. Peters, M. Fornage, T. L. Assimes, E. A. Whitsel, D. Levy, A. A. Baccarelli

Dipartimento di Scienze della Salute

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

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.

Lingua originale	Inglese
pagine (da-a)	645-657
Numero di pagine	13
Rivista	Circulation
Volume	140
Numero di pubblicazione	8
DOI	https://doi.org/10.1161/CIRCULATIONAHA.118.039357
Stato di pubblicazione	Pubblicato - 2019

Keywords

coronary artery disease
coronary heart disease
epigenetics
gene expression regulation
genomics

Accesso al documento

10.1161/CIRCULATIONAHA.118.039357

https://hdl.handle.net/11579/200115

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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., ... Baccarelli, A. A. (2019). Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. Circulation, 140(8), 645-657. https://doi.org/10.1161/CIRCULATIONAHA.118.039357

@article{9a6d8f7993ce46ebb9ea2a5e9f40dd8b,

title = "Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease",

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.",

keywords = "coronary artery disease, coronary heart disease, epigenetics, gene expression regulation, genomics, coronary artery disease, coronary heart disease, epigenetics, gene expression regulation, genomics",

author = "G. Agha and Mendelson, {M. M.} and Ward-Caviness, {C. K.} and R. Joehanes and T. Huan and R. Gondalia and E. Salfati and Brody, {J. A.} and G. Fiorito and J. Bressler and Chen, {B. H.} and S. Ligthart and S. Guarrera and E. Colicino and Just, {A. C.} and S. Wahl and C. Gieger and Vandiver, {A. R.} and T. Tanaka and Hernandez, {D. G.} and Pilling, {L. C.} and Singleton, {A. B.} and Carlotta SACERDOTE and V. Krogh and S. Panico and R. Tumino and Y. Li and G. Zhang and Stewart, {J. D.} and Floyd, {J. S.} and Wiggins, {K. L.} and Rotter, {J. I.} and M. Multhaup and K. Bakulski and S. Horvath and Tsao, {P. S.} and Absher, {D. M.} and P. Vokonas and J. Hirschhorn and Fallin, {M. D.} and C. Liu and S. Bandinelli and E. Boerwinkle and A. Dehghan and Schwartz, {J. D.} and Psaty, {B. M.} and Feinberg, {A. P.} and L. Hou and L. Ferrucci and N. Sotoodehnia and G. Matullo and A. Peters and M. Fornage and Assimes, {T. L.} and Whitsel, {E. A.} and D. Levy and Baccarelli, {A. A.}",

year = "2019",

doi = "10.1161/CIRCULATIONAHA.118.039357",

language = "English",

volume = "140",

pages = "645--657",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "8",

}

Agha, G, Mendelson, MM, Ward-Caviness, CK, Joehanes, R, Huan, T, Gondalia, R, Salfati, E, Brody, JA, Fiorito, G, Bressler, J, Chen, BH, Ligthart, S, Guarrera, S, Colicino, E, Just, AC, Wahl, S, Gieger, C, Vandiver, AR, Tanaka, T, Hernandez, DG, Pilling, LC, Singleton, AB, SACERDOTE, C, Krogh, V, Panico, S, Tumino, R, Li, Y, Zhang, G, Stewart, JD, Floyd, JS, Wiggins, KL, Rotter, JI, Multhaup, M, Bakulski, K, Horvath, S, Tsao, PS, Absher, DM, Vokonas, P, Hirschhorn, J, Fallin, MD, Liu, C, Bandinelli, S, Boerwinkle, E, Dehghan, A, Schwartz, JD, Psaty, BM, Feinberg, AP, Hou, L, Ferrucci, L, Sotoodehnia, N, Matullo, G, Peters, A, Fornage, M, Assimes, TL, Whitsel, EA, Levy, D & Baccarelli, AA 2019, 'Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease', Circulation, vol. 140, n. 8, pagg. 645-657. https://doi.org/10.1161/CIRCULATIONAHA.118.039357

TY - JOUR

T1 - Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

AU - Agha, G.

AU - Mendelson, M. M.

AU - Ward-Caviness, C. K.

AU - Joehanes, R.

AU - Huan, T.

AU - Gondalia, R.

AU - Salfati, E.

AU - Brody, J. A.

AU - Fiorito, G.

AU - Bressler, J.

AU - Chen, B. H.

AU - Ligthart, S.

AU - Guarrera, S.

AU - Colicino, E.

AU - Just, A. C.

AU - Wahl, S.

AU - Gieger, C.

AU - Vandiver, A. R.

AU - Tanaka, T.

AU - Hernandez, D. G.

AU - Pilling, L. C.

AU - Singleton, A. B.

AU - SACERDOTE, Carlotta

AU - Krogh, V.

AU - Panico, S.

AU - Tumino, R.

AU - Li, Y.

AU - Zhang, G.

AU - Stewart, J. D.

AU - Floyd, J. S.

AU - Wiggins, K. L.

AU - Rotter, J. I.

AU - Multhaup, M.

AU - Bakulski, K.

AU - Horvath, S.

AU - Tsao, P. S.

AU - Absher, D. M.

AU - Vokonas, P.

AU - Hirschhorn, J.

AU - Fallin, M. D.

AU - Liu, C.

AU - Bandinelli, S.

AU - Boerwinkle, E.

AU - Dehghan, A.

AU - Schwartz, J. D.

AU - Psaty, B. M.

AU - Feinberg, A. P.

AU - Hou, L.

AU - Ferrucci, L.

AU - Sotoodehnia, N.

AU - Matullo, G.

AU - Peters, A.

AU - Fornage, M.

AU - Assimes, T. L.

AU - Whitsel, E. A.

AU - Levy, D.

AU - Baccarelli, A. A.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - coronary artery disease

KW - coronary heart disease

KW - epigenetics

KW - gene expression regulation

KW - genomics

KW - coronary artery disease

KW - coronary heart disease

KW - epigenetics

KW - gene expression regulation

KW - genomics

UR - https://iris.uniupo.it/handle/11579/200115

U2 - 10.1161/CIRCULATIONAHA.118.039357

DO - 10.1161/CIRCULATIONAHA.118.039357

M3 - Article

SN - 0009-7322

VL - 140

SP - 645

EP - 657

JO - Circulation

JF - Circulation

IS - 8

ER -

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease

Abstract

Keywords

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