DNA methylation-based measures of biological age: meta-analysis predicting time to death.

TitleDNA methylation-based measures of biological age: meta-analysis predicting time to death.
Publication TypeJournal Article
Year of Publication2016
AuthorsChen, BH, Marioni, RE, Colicino, E, Peters, MJ, Ward-Caviness, CK, Tsai, P-C, Roetker, NS, Just, AC, Demerath, EW, Guan, W, Bressler, J, Fornage, M, Studenski, S, Vandiver, AR, Moore, AZenobia, Tanaka, T, Kiel, DP, Liang, L, Vokonas, P, Schwartz, J, Lunetta, KL, Murabito, JM, Bandinelli, S, Hernandez, DG, Melzer, D, Nalls, M, Pilling, LC, Price, TR, Singleton, AB, Gieger, C, Holle, R, Kretschmer, A, Kronenberg, F, Kunze, S, Linseisen, J, Meisinger, C, Rathmann, W, Waldenberger, M, Visscher, PM, Shah, S, Wray, NR, McRae, AF, Franco, OH, Hofman, A, Uitterlinden, AG, Absher, D, Assimes, T, Levine, ME, Lu, AT, Tsao, PS, Hou, L, Manson, JAE, Carty, CL, LaCroix, AZ, Reiner, AP, Spector, TD, Feinberg, AP, Levy, D, Baccarelli, A, van Meurs, J, Bell, JT, Peters, A, Deary, IJ, Pankow, JS, Ferrucci, L, Horvath, S
JournalAging (Albany NY)
Volume8
Issue9
Pagination1844-1865
Date Published2016 Sep 28
ISSN1945-4589
KeywordsAging, DNA Methylation, Epigenesis, Genetic, Female, Humans, Logistic Models, Male, Mortality, Racial Groups, Risk Factors, Survival Analysis, T-Lymphocyte Subsets
Abstract

Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality (p≤8.2x10, independent of chronological age, even after adjusting for additional risk factors (p<5.4x10, and within the racial/ethnic groups that we examined (non-Hispanic whites, Hispanics, African Americans). Epigenetic age estimates that incorporated information on blood cell composition led to the smallest p-values for time to death (p=7.5x10). Overall, this study a) strengthens the evidence that epigenetic age predicts all-cause mortality above and beyond chronological age and traditional risk factors, and b) demonstrates that epigenetic age estimates that incorporate information on blood cell counts lead to highly significant associations with all-cause mortality.

DOI10.18632/aging.101020
Alternate JournalAging (Albany NY)
PubMed ID27690265
PubMed Central IDPMC5076441
Grant ListHHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
MR/M013111/1 / MRC_ / Medical Research Council / United Kingdom
R01 ES015172 / ES / NIEHS NIH HHS / United States
R01 ES025225 / ES / NIEHS NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
P30 ES023515 / ES / NIEHS NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
U34 AG051425 / AG / NIA NIH HHS / United States
R01 AG042511 / AG / NIA NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
HHSN268201100012C / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
RF1 AG036042 / AG / NIA NIH HHS / United States
T32 GM007309 / GM / NIGMS NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
/ BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
HHSN268201100003C / WH / WHI NIH HHS / United States
/ RA / ARRA NIH HHS / United States
R01 ES021733 / ES / NIEHS NIH HHS / United States
R01 AG042187 / AG / NIA NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
R01 AG029451 / AG / NIA NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
/ CSO_ / Chief Scientist Office / United Kingdom
/ WT_ / Wellcome Trust / United Kingdom
HHSN268201100001C / WH / WHI NIH HHS / United States
R00 ES023450 / ES / NIEHS NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States

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