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Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.
Tuesday,2020-10-27 18:13 America/Los_Angeles — ecterry
| Title | Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | 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, 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 |
| Journal | Circulation |
| Volume | 140 |
| Issue | 8 |
| Pagination | 645-657 |
| Date Published | 2019 08 20 |
| ISSN | 1524-4539 |
| Keywords | Adult, Aged, Cohort Studies, Coronary Disease, CpG Islands, DNA Methylation, Europe, Female, Genome-Wide Association Study, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Population Groups, Prognosis, Prospective Studies, Risk, United States |
| Abstract | <p><b>BACKGROUND: </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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSION: </b>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.</p> |
| DOI | 10.1161/CIRCULATIONAHA.118.039357 |
| Alternate Journal | Circulation |
| PubMed ID | 31424985 |
| PubMed Central ID | PMC6812683 |
| Grant List | RC2 HL102419 / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201100004I / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States HHSN268201100002C / WH / WHI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States HHSN268201100001I / HL / NHLBI NIH HHS / United States R01 ES015172 / ES / NIEHS NIH HHS / United States R01 ES025225 / ES / NIEHS NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States R01 ES020836 / ES / NIEHS NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 MD009164 / MD / NIMHD NIH HHS / United States HHSN268200800007C / HL / 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 N01 HC025195 / HC / 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 N01 HC085082 / HC / NHLBI NIH HHS / United States R01 MD013299 / MD / NIMHD NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States HHSN268201700002C / HL / NHLBI 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 R21 ES020010 / ES / NIEHS NIH HHS / United States R01 ES027747 / ES / NIEHS NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States HHSN268201700001C / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268201700003C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States HHSN268201700004C / HL / NHLBI NIH HHS / United States HHSN268201100003I / HL / NHLBI NIH HHS / United States HHSN268201100002I / 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 N01HC85080 / HL / NHLBI NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States HHSN268201100001C / WH / WHI NIH HHS / United States HHSN268201100004C / WH / WHI NIH HHS / United States K99 HL136875 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States P30 ES009089 / ES / NIEHS NIH HHS / United States |
ePub date:
19/08