Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models

Abstract Objective Epigenetic aging has been confirmed to be associated with the pathogenesis of rheumatoid arthritis (RA), however, its role in the prognosis of RA remains unclear. Methods In this cross-sectional and prospective study, Epigenetic age and acceleration in participants of the National...

Full description

Saved in:
Bibliographic Details
Main Authors: Yuhang Ou, Zhihao Wang, Yunbo Yuan, Yuze He, Wenhao Li, Hao Ren, Junhong Li, Siliang Chen, Yanhui Liu
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Clinical Epigenetics
Subjects:
Online Access:https://doi.org/10.1186/s13148-025-01919-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849238318071414784
author Yuhang Ou
Zhihao Wang
Yunbo Yuan
Yuze He
Wenhao Li
Hao Ren
Junhong Li
Siliang Chen
Yanhui Liu
author_facet Yuhang Ou
Zhihao Wang
Yunbo Yuan
Yuze He
Wenhao Li
Hao Ren
Junhong Li
Siliang Chen
Yanhui Liu
author_sort Yuhang Ou
collection DOAJ
description Abstract Objective Epigenetic aging has been confirmed to be associated with the pathogenesis of rheumatoid arthritis (RA), however, its role in the prognosis of RA remains unclear. Methods In this cross-sectional and prospective study, Epigenetic age and acceleration in participants of the National Health and Nutrition Examination Survey (NHANES) were calculated with Horvath’s clock, Hannum’s clock, PhenoAge, GrimAge, and GrimAge version 2 (GrimAge2). The association of epigenetic age and epigenetic age acceleration with the prevalence and overall mortality risk in RA was assessed with prediction models constructed. Results Accelerated epigenetic aging increased the risk of overall mortality in RA with hazard ratio of 1.075 (95% CI 1.043–1.107, p < 0.0001) for GrimAge2 acceleration (GrimAge2Accel) and 1.064 (1.032–1.098, p < 0.0001) for GrimAge acceleration (GrimAgeAccel). The GrimAge2Accel-based models, adjusted for a set of covariates composed of independent risk factors, excelled in predicting the 10 year and 20 year survival with area under curve of 0.760 (95% CI 0.621–0.898) and 0.823 (0.697–0.949), respectively. Conclusion Epigenetic aging may play a harmfully promotive role in the onset and progression of RA, and the GrimAge2Accel-based prediction models could effectively predict the survival of RA patients. Further research is needed to elucidate the underlying mechanisms and to explore the potential clinical implications.
format Article
id doaj-art-9cce697b7bb54721ab2f89e7ce096892
institution Kabale University
issn 1868-7083
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Clinical Epigenetics
spelling doaj-art-9cce697b7bb54721ab2f89e7ce0968922025-08-20T04:01:41ZengBMCClinical Epigenetics1868-70832025-07-0117111310.1186/s13148-025-01919-8Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction modelsYuhang Ou0Zhihao Wang1Yunbo Yuan2Yuze He3Wenhao Li4Hao Ren5Junhong Li6Siliang Chen7Yanhui Liu8Department of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityAbstract Objective Epigenetic aging has been confirmed to be associated with the pathogenesis of rheumatoid arthritis (RA), however, its role in the prognosis of RA remains unclear. Methods In this cross-sectional and prospective study, Epigenetic age and acceleration in participants of the National Health and Nutrition Examination Survey (NHANES) were calculated with Horvath’s clock, Hannum’s clock, PhenoAge, GrimAge, and GrimAge version 2 (GrimAge2). The association of epigenetic age and epigenetic age acceleration with the prevalence and overall mortality risk in RA was assessed with prediction models constructed. Results Accelerated epigenetic aging increased the risk of overall mortality in RA with hazard ratio of 1.075 (95% CI 1.043–1.107, p < 0.0001) for GrimAge2 acceleration (GrimAge2Accel) and 1.064 (1.032–1.098, p < 0.0001) for GrimAge acceleration (GrimAgeAccel). The GrimAge2Accel-based models, adjusted for a set of covariates composed of independent risk factors, excelled in predicting the 10 year and 20 year survival with area under curve of 0.760 (95% CI 0.621–0.898) and 0.823 (0.697–0.949), respectively. Conclusion Epigenetic aging may play a harmfully promotive role in the onset and progression of RA, and the GrimAge2Accel-based prediction models could effectively predict the survival of RA patients. Further research is needed to elucidate the underlying mechanisms and to explore the potential clinical implications.https://doi.org/10.1186/s13148-025-01919-8Epigenetic age accelerationRheumatoid arthritisNHANESCross-sectional and prospective study
spellingShingle Yuhang Ou
Zhihao Wang
Yunbo Yuan
Yuze He
Wenhao Li
Hao Ren
Junhong Li
Siliang Chen
Yanhui Liu
Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
Clinical Epigenetics
Epigenetic age acceleration
Rheumatoid arthritis
NHANES
Cross-sectional and prospective study
title Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
title_full Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
title_fullStr Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
title_full_unstemmed Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
title_short Epigenetic age acceleration and rheumatoid arthritis: an NHANES-based analysis and survival prediction models
title_sort epigenetic age acceleration and rheumatoid arthritis an nhanes based analysis and survival prediction models
topic Epigenetic age acceleration
Rheumatoid arthritis
NHANES
Cross-sectional and prospective study
url https://doi.org/10.1186/s13148-025-01919-8
work_keys_str_mv AT yuhangou epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT zhihaowang epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT yunboyuan epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT yuzehe epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT wenhaoli epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT haoren epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT junhongli epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT siliangchen epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels
AT yanhuiliu epigeneticageaccelerationandrheumatoidarthritisannhanesbasedanalysisandsurvivalpredictionmodels