Epigenome-wide analysis of frailty : Results from two European twin cohorts
Mak, Jonathan K.L.; Skovgaard, Asmus Cosmos; Nygaard, Marianne; Kananen, Laura; Reynolds, Chandra A.; Wang, Yunzhang; Kuja-Halkola, Ralf; Karlsson, Ida K.; Pedersen, Nancy L.; Hägg, Sara; Soerensen, Mette; Jylhävä, Juulia (2024-06)
Mak, Jonathan K.L.
Skovgaard, Asmus Cosmos
Nygaard, Marianne
Kananen, Laura
Reynolds, Chandra A.
Wang, Yunzhang
Kuja-Halkola, Ralf
Karlsson, Ida K.
Pedersen, Nancy L.
Hägg, Sara
Soerensen, Mette
Jylhävä, Juulia
06 / 2024
e14135
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202404123517
https://urn.fi/URN:NBN:fi:tuni-202404123517
Kuvaus
Peer reviewed
Tiivistelmä
Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age-related state of physiological decline. In this study, we performed a meta-analysis of epigenome-wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta-analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age-related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed-effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta-analysis results replicated 34 of the 77 previously reported frailty-associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty.
Kokoelmat
- TUNICRIS-julkaisut [19236]