Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults

Xiangwei Li, Thomas Delerue, Ben Schöttker, Bernd Holleczek, Eva Grill, Annette Peters, Melanie Waldenberger, Barbara Thorand and Hermann Brenner ()
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Xiangwei Li: German Cancer Research Center (DKFZ)
Thomas Delerue: German Research Center for Environmental Health
Ben Schöttker: German Cancer Research Center (DKFZ)
Bernd Holleczek: Krebsregister Saarland
Eva Grill: Ludwig-Maximilians-Universität München
Annette Peters: German Research Center for Environmental Health
Melanie Waldenberger: German Research Center for Environmental Health
Barbara Thorand: Ludwig-Maximilians-Universität München
Hermann Brenner: German Cancer Research Center (DKFZ)

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-32893-x

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