AU  - Li, Xiangwei
AU  - Delerue, Thomas
AU  - Schöttker, Ben
AU  - Holleczek, Bernd
AU  - Grill, Eva
AU  - Peters, Annette
AU  - Waldenberger, Melanie
AU  - Thorand, Barbara
AU  - Brenner, Hermann
TI  - Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults.
JO  - Nature Communications
VL  - 13
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2022-02111
SP  - 5269
PY  - 2022
N1  - #EA:C070#LA:C070#LA:C120#
AB  - DNA methylation (DNAm) patterns in peripheral blood have been shown to be associated with aging related health outcomes. We perform an epigenome-wide screening to identify CpGs related to frailty, defined by a frailty index (FI), in a large population-based cohort of older adults from Germany, the ESTHER study. Sixty-five CpGs are identified as frailty related methylation loci. Using LASSO regression, 20 CpGs are selected to derive a DNAm based algorithm for predicting frailty, the epigenetic frailty risk score (eFRS). The eFRS exhibits strong associations with frailty at baseline and after up to five-years of follow-up independently of established frailty risk factors. These associations are confirmed in another independent population-based cohort study, the KORA-Age study, conducted in older adults. In conclusion, we identify 65 CpGs as frailty-related loci, of which 20 CpGs are used to calculate the eFRS with predictive performance for frailty over long-term follow-up.
LB  - PUB:(DE-HGF)16
C6  - pmid:36071044
DO  - DOI:10.1038/s41467-022-32893-x
UR  - https://inrepo02.dkfz.de/record/181611
ER  -