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@ARTICLE{Gao:141672,
author = {X. Gao$^*$ and Y. Zhang$^*$ and U. Mons$^*$ and H.
Brenner$^*$},
title = {{L}eukocyte telomere length and epigenetic-based mortality
risk score: associations with all-cause mortality among
older adults.},
journal = {Epigenetics},
volume = {13},
number = {8},
issn = {1559-2308},
address = {Austin, Tex.},
publisher = {Landes Bioscience},
reportid = {DKFZ-2018-01943},
pages = {846 - 857},
year = {2018},
abstract = {Telomere length (TL) has been established as a biomarker of
aging and aging-related health outcomes, but showed only a
weak or inconsistent association with all-cause mortality in
previous epidemiological studies. Recently, an epigenetic
'mortality risk score' (MS) based on whole blood DNA
methylation at 10 mortality-related CpG sites has been
demonstrated to be strongly related to all-cause mortality
at the population level. This study aimed to address the
association between TL and this MS, and to assess and
compare their associations with all-cause mortality. The MS
was derived from the DNA methylation profiles measured by
Illumina Human Methylation450K Beadchip and TL was measured
by quantitative PCR at baseline among 1517 participants aged
50-75 of the German ESTHER cohort study. In cross-sectional
bi- and multivariable analyses, the MS was strongly
associated and showed monotonic dose-response relationships
with TL (p-values <0.05). However, only the MS but not TL
was associated with all-cause mortality during a median
follow-up of 12.5 years. After controlling for potential
covariates and TL, hazard ratios $(95\%$ CI) for all-cause
mortality for low, moderate and high levels of the MS
defined by 1, 2-5 and >5 CpG sites with aberrant methylation
were 2.24 (1.13-4.41), 3.31 (1.76-6.22) and 6.33
(3.22-12.41) compared to a MS of 0, respectively. Our
investigation shows that the epigenetic-based MS is strongly
associated with TL, a broadly accepted aging biomarker, and
at the same time shows much stronger associations with
all-cause mortality than the latter.},
cin = {C070 / G110 / M050},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)G110-20160331 /
I:(DE-He78)M050-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30152726},
pmc = {pmc:PMC6224222},
doi = {10.1080/15592294.2018.1514853},
url = {https://inrepo02.dkfz.de/record/141672},
}