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Colicino, E.* ; Marioni, R.* ; Ward-Caviness, C.K. ; Gondalia, R.* ; Guan, W.* ; Chen, B.* ; Tsai, P.C.* ; Huan, T.* ; Xu, G.* ; Golareh, A.* ; Schwartz, J.* ; Vokonas, P.* ; Just, A.* ; Starr, J.M.* ; McRae, A.F.* ; Wray, N.R.* ; Visscher, P.M.* ; Bressler, J.* ; Zhang, W.* ; Tanaka, T.* ; Moore, A.Z.* ; Pilling, L.C.* ; Zhang, G.* ; Stewart, J.D.* ; Li, Y.* ; Hou, L.* ; Castillo-Fernandez, J.* ; Spector, T.* ; Kiel, D.P.* ; Murabito, J.M.* ; Liu, C.* ; Mendelson, M.* ; Assimes, T.* ; Absher, D.* ; Tsaho, P.S.* ; Lu, A.T.* ; Ferrucci, L.* ; Wilson, R. ; Waldenberger, M. ; Prokisch, H. ; Bandinelli, S.* ; Bell, J.T.* ; Levy, D.* ; Deary, I.J.* ; Horvath, S.* ; Pankow, J.* ; Peters, A. ; Whitsel, E.A.* ; Baccarelli, A.*

Blood DNA methylation sites predict death risk in a longitudinal study of 12,300 individuals.

Aging 12, 14092-14124 (2020)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P < 9.3x10-7) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)-mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions-were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)-mapping respectively to SERINC2, CHST12, and an intergenic region-were associated with increased mortality risk. DNA methylation at each site predicted 5%-15% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by using Mendelian randomization, identifying weak causal relationship between cg18424841 and cg09615688 with coronary heart disease. Of the nine sites, three (cg20045320, cg07839457, cg07677157) were associated with lower incidence of heart disease risk and two (cg20045320, cg07839457) with smoking and inflammation in prior CHARGE analyses. Methylation of cg20045320, cg07839457, and cg17086398 was associated with decreased expression of nearby genes (IFITM3, IRF, NLRC5, MT1, MT2, MARCKSL1) linked to immune responses and cardiometabolic diseases. These sites may serve as useful clinical tools for mortality risk assessment and preventative care.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 450k ; Dna Methylation ; Aging ; All-cause Mortality ; Epigenome-wide Association Studies
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 1945-4589
e-ISSN 1945-4589
Zeitschrift Aging
Quellenangaben Band: 12, Heft: 14, Seiten: 14092-14124 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Neurogenomics (ING)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504000-010
G-504091-001
G-503292-001
DOI 10.18632/aging.103408
Scopus ID 85088842670
PubMed ID 32697766
Erfassungsdatum 2020-09-16
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