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Research Article

DNA methylation marker identification and poly-methylation risk score in prediction of healthspan termination

    Meiqi Yang‡

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Mei Wang‡

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Xiaoyu Zhao‡

    Department of Statistics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Feifei Xu

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ,
    Shuang Liang

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ,
    Yifan Wang

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ,
    Nanxi Wang

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ,
    Muhammed Lamin Sambou

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    ,
    Yue Jiang

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Collaborative Innovation Center for Cancer Personalized Medicine & China International Cooperation Center for Environment & Human Health, Gusu School, Nanjing Medical University, Nanjing, 211166, China

    &
    Juncheng Dai

    *Author for correspondence:

    E-mail Address: djc@njmu.edu.cn

    Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Collaborative Innovation Center for Cancer Personalized Medicine & China International Cooperation Center for Environment & Human Health, Gusu School, Nanjing Medical University, Nanjing, 211166, China

    Published Online:https://doi.org/10.2217/epi-2023-0343

    Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13–1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.

    Tweetable abstract

    The concept of the ‘healthspan’, the time an individual remains morbidity-free, requires more attention. Poly-methylation risk scores have a promising application in discriminating subpopulations at risk of healthspan termination to facilitate early prevention.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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