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

 
TitleBlood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.
Publication TypeJournal Article
Year of Publication2019
AuthorsAgha, 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, M Fallin, D, 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
JournalCirculation
Volume140
Issue8
Pagination645-657
Date Published2019 Aug 20
ISSN1524-4539
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

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.

DOI10.1161/CIRCULATIONAHA.118.039357
Alternate JournalCirculation
PubMed ID31424985
PubMed Central IDPMC6812683
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 ES015172 / ES / NIEHS NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 ES025225 / ES / NIEHS NIH HHS / United States
R01 ES020836 / ES / NIEHS NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
R01 ES021733 / ES / NIEHS NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R21 ES020010 / ES / NIEHS NIH HHS / United States
R01 ES027747 / ES / NIEHS NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201300006C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 ES014663 / ES / NIEHS NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
P30 ES009089 / ES / NIEHS NIH HHS / United States