Skip to main content

Biomarkers in Clinical Epigenetics

Edited by
Dawn L. DeMeo, MD, MPH, Brigham and Women's Hospital/ Harvard Medical School, USA
James M Flanagan, PhD, Imperial College London, UK
Harold Snieder, PhD, University Medical Center Groningen, The Netherlands
Bea Wisman, PhD, University Medical Center Groningen, The Netherlands
Tomasz K Wojdacz, PhD, Pomeranian Medical University, Poland

New Content Item





Epigenetic biomarkers have significantly contributed to improved understanding of the origins and progression of disease. Moreover, increasing evidence shows that epigenetic biomarkers have potential for personalized medicine. However, routine use of epigenetic biomarkers in in-vitro diagnostics (IVD) is lagging behind the discoveries of new biomarkers. In this thematic series of Clinical Epigenetics, we discuss current progress in development of epigenetic biomarkers for clinical use in common complex diseases of ageing and welcome both original research and reviews.

The sections of the collection include:

1. Types of epigenetic biomarkers and readiness for IVD use

  1. DNA methylation as biomarker
  2. Histone modification as biomarker
  3. Upcoming field of circulating free nucleosomes as biomarker


2. Progress towards clinical use of biomarker

  1. Biomarkers of environmental exposures and causality of the biomarker
  2. Disease predisposition biomarkers
  3. Biomarkers used for disease detection
  4. Clinical disease prevention and management: predictive and prognostic
  5. Monitoring of chronic disease


3. Single versus multiple biomarkers and risk scores

4. Major stages of clinical validation of the biomarker

5. Biomarker detection technologies suitable for IVD use and significance of bioinformatics

6. Ethics and regulatory aspects of IVD epigenetic biomarkers

This collection of articles has not been sponsored and articles have undergone the journal’s standard peer-review process. Please find out more about our journal and its policies, here. This collection is closed for submissions.


  1. DNA methylation clocks emerged as a tool to determine biological aging and have been related to mortality and age-related diseases. Little is known about the association of DNA methylation age (DNAm age) with ...

    Authors: Jiahui Si, Lu Chen, Canqing Yu, Yu Guo, Dianjianyi Sun, Yuanjie Pang, Iona Y. Millwood, Robin G. Walters, Ling Yang, Yiping Chen, Huaidong Du, Shixian Feng, Xiaoming Yang, Daniel Avery, Junshi Chen, Zhengming Chen…
    Citation: Clinical Epigenetics 2023 15:52
    Content type: Research Published on:

  2. In peripheral blood, DNA methylation (DNAm) patterns in inflammatory bowel disease patients reflect inflammatory status rather than disease status. Here, we examined DNAm in diseased rectal mucosa from ulcerat...

    Authors: Suresh Venkateswaran, Hari K. Somineni, Jason D. Matthews, Varun Kilaru, Jeffrey S. Hyams, Lee A. Denson, Richard Kellamayer, Greg Gibson, David J. Cutler, Karen N. Conneely, Alicia K. Smith and Subra Kugathasan
    Citation: Clinical Epigenetics 2023 15:50
    Content type: Research Published on:

  3. Changes in gene-specific promoter methylation may result from aging and environmental influences. Atherosclerosis is associated with aging and environmental effects. Thus, promoter methylation profiling may be...

    Authors: Jee Yeon Kim, Jaroslav Jelinek, Young Ho Lee, Dae Hyun Kim, Keunsoo Kang, Su Hyun Ryu, Hye Rin Moon, Kwangjo Cho, Seo Hee Rha, Jae Kwan Cha, Jean-Pierre J. Issa and Jei Kim
    Citation: Clinical Epigenetics 2023 15:11
    Content type: Research Published on:

  4. The variation in multiple sclerosis (MS) disease severity is incompletely explained by genetics, suggesting genetic and environmental interactions are involved. Moreover, the lack of prognostic biomarkers make...

    Authors: Maria Pia Campagna, Alexandre Xavier, Rodney A. Lea, Jim Stankovich, Vicki E. Maltby, Helmut Butzkueven, Jeannette Lechner-Scott, Rodney J. Scott and Vilija G. Jokubaitis
    Citation: Clinical Epigenetics 2022 14:194
    Content type: Research Published on:

  5. Fetal overgrowth “programs” an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in pl...

    Authors: Meng-Nan Yang, Rong Huang, Tao Zheng, Yu Dong, Wen-Juan Wang, Ya-Jie Xu, Vrati Mehra, Guang-Di Zhou, Xin Liu, Hua He, Fang Fang, Fei Li, Jian-Gao Fan, Jun Zhang, Fengxiu Ouyang, Laurent Briollais…
    Citation: Clinical Epigenetics 2022 14:192
    Content type: Research Published on:

  6. Stroke is the leading cause of mortality in China. DNA methylation has essential roles in multiple diseases, but its association with stroke was barely studied. We hereby explored the association between blood...

    Authors: Chunlan Liu, Mengxia Li, Qiming Yin, Yao Fan, Chong Shen and Rongxi Yang
    Citation: Clinical Epigenetics 2022 14:191
    Content type: Research Published on:

    The Correction to this article has been published in Clinical Epigenetics 2023 15:141

  7. The death rate of lung cancer (LC) ranks first in the world. Changes of DNA methylation in peripheral blood may be related to malignant tumors. It is necessary to explore blood-based biomarkers of methylation ...

    Authors: Yifei Fang, Yunhui Qu, Longtao Ji, Hao Sun, Jiaqi Li, Yutong Zhao, Feifei Liang, Zhi Wang, Jiao Su, Jingjing Liu, Liping Dai and Songyun Ouyang
    Citation: Clinical Epigenetics 2022 14:167
    Content type: Research Published on:

  8. Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic ch...

    Authors: Jonviea D. Chamberlain, Sébastien Nusslé, Laurence Chapatte, Cassandre Kinnaer, Dusan Petrovic, Sylvain Pradervand, Murielle Bochud, Sarah E. Harris, Janie Corley, Simon R. Cox and Semira Gonseth Nusslé
    Citation: Clinical Epigenetics 2022 14:155
    Content type: Research Published on:

  9. Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV te...

    Authors: Chiara Herzog, Karin Sundström, Allison Jones, Iona Evans, James E. Barrett, Jiangrong Wang, Elisa Redl, Lena Schreiberhuber, Laura Costas, Sonia Paytubi, Lukas Dostalek, Michal Zikan, David Cibula, Gaby Sroczynski, Uwe Siebert, Joakim Dillner…
    Citation: Clinical Epigenetics 2022 14:150
    Content type: Research Published on:

  10. Epigenetic modifications offer compelling evidence of the environmental etiology of complex diseases. Social and biographical conditions, as well as material exposures, all modulate our biology with consequenc...

    Authors: Luca Chiapperino and Francesco Paneni
    Citation: Clinical Epigenetics 2022 14:144
    Content type: Correspondence Published on:

    The Correspondence to this article has been published in Epigenetics Communications 2023 3:4

    The Correspondence to this article has been published in Epigenetics Communications 2023 3:2

  11. The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in ...

    Authors: Natalia Cullell, Carolina Soriano-Tárraga, Cristina Gallego-Fábrega, Jara Cárcel-Márquez, Elena Muiño, Laia Llucià-Carol, Miquel Lledós, Manel Esteller, Manuel Castro de Moura, Joan Montaner, Anna Rosell, Pilar Delgado, Joan Martí-Fábregas, Jerzy Krupinski, Jaume Roquer, Jordi Jiménez-Conde…
    Citation: Clinical Epigenetics 2022 14:124
    Content type: Research Published on:

  12. DNA methylation-regulated genes have been demonstrated as the crucial participants in the occurrence of coronary heart disease (CHD). The machine learning based on DNA methylation-regulated genes has tremendou...

    Authors: Xiaokang Zhang, Chen Wang, Dingdong He, Yating Cheng, Li Yu, Daoxi Qi, Boyu Li and Fang Zheng
    Citation: Clinical Epigenetics 2022 14:122
    Content type: Research Published on:

  13. Over the past decade, bioethicists, legal scholars and social scientists have started to investigate the potential implications of epigenetic research and technologies on medicine and society. There is growing...

    Authors: Charles Dupras, Terese Knoppers, Nicole Palmour, Elisabeth Beauchamp, Stamatina Liosi, Reiner Siebert, Alison May Berner, Stephan Beck, Ian Charest and Yann Joly
    Citation: Clinical Epigenetics 2022 14:110
    Content type: Research Published on:

  14. DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavior...

    Authors: Kyeezu Kim, Yinan Zheng, Brian T. Joyce, Hongmei Jiang, Philip Greenland, David R. Jacobs Jr., Kai Zhang, Lei Liu, Norrina B. Allen, John T. Wilkins, Sarah N. Forrester, Donald M. Lloyd-Jones and Lifang Hou
    Citation: Clinical Epigenetics 2022 14:85
    Content type: Research Published on:

  15. Ovarian cancer (OC) is a highly lethal gynecologic cancer, and it is hard to diagnose at an early stage. Clinically, there are no ovarian cancer-specific markers for early detection. Here, we demonstrate the u...

    Authors: Huaiwu Lu, Yunyun Liu, Jingyu Wang, Shaliu Fu, Lingping Wang, Chunxian Huang, Jing Li, Lingling Xie, Dongyan Wang, Dan Li, Hui Zhou and Qunxian Rao
    Citation: Clinical Epigenetics 2022 14:74
    Content type: Research Published on:

  16. DNA methylation biomarkers for early detection, risk stratification and treatment response in cancer have been of great interest over the past decades. Nevertheless, clinical implementation of these biomarkers...

    Authors: Maartje Massen, Kim Lommen, Kim A. D. Wouters, Johan Vandersmissen, Wim van Criekinge, James G. Herman, Veerle Melotte, Leo J. Schouten, Manon van Engeland and Kim M. Smits
    Citation: Clinical Epigenetics 2022 14:56
    Content type: Methodology Published on:

  19. Multiple studies have reported the prognostic impact of DNA methylation changes in acute myeloid leukemia (AML). However, these epigenetic markers have not been thoroughly validated and therefore are still not...

    Authors: Šárka Šestáková, Ela Cerovská, Cyril Šálek, Dávid Kundrát, Ivana Ježíšková, Adam Folta, Jiří Mayer, Zdeněk Ráčil, Petr Cetkovský and Hana Remešová
    Citation: Clinical Epigenetics 2022 14:22
    Content type: Research Published on:

  20. Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant compli...

    Authors: Iacopo Cristoferi, Tommaso Antonio Giacon, Karin Boer, Myrthe van Baardwijk, Flavia Neri, Manuela Campisi, Hendrikus J. A. N. Kimenai, Marian C. Clahsen - van Groningen, Sofia Pavanello, Lucrezia Furian and Robert C. Minnee
    Citation: Clinical Epigenetics 2022 14:20
    Content type: Review Published on:

  21. Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age accel...

    Authors: Rhona A. Beynon, Suzanne M. Ingle, Ryan Langdon, Margaret May, Andy Ness, Richard M. Martin, Matthew Suderman, Kate Ingarfield, Riccardo E. Marioni, Daniel L. McCartney, Tim Waterboer, Michael Pawlita, Caroline Relton, George Davey Smith and Rebecca C. Richmond
    Citation: Clinical Epigenetics 2022 14:1
    Content type: Research Published on:

  22. Circulating tumor DNA (ctDNA) is a promising diagnostic and prognostic marker for many cancers and has been actively investigated in recent years. Previous studies have already demonstrated the potential use o...

    Authors: Wu-Hao Lin, Jian Xiao, Zi-Yi Ye, Da-Liang Wei, Xiao-Hui Zhai, Rui-Hua Xu, Zhao-Lei Zeng and Hui-Yan Luo
    Citation: Clinical Epigenetics 2021 13:232
    Content type: Research Published on:

  23. Metformin and weight loss relationships with epigenetic age measures—biological aging biomarkers—remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese br...

    Authors: Jamaji C. Nwanaji-Enwerem, Felicia Fei-Lei Chung, Lars Van der Laan, Alexei Novoloaca, Cyrille Cuenin, Harriet Johansson, Bernardo Bonanni, Alan E. Hubbard, Martyn T. Smith, Sheri J. Hartman, Andres Cardenas, Dorothy D. Sears and Zdenko Herceg
    Citation: Clinical Epigenetics 2021 13:224
    Content type: Short report Published on:

  24. Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression a...

    Authors: Jian Zhou, Tong Cheng, Xing Li, Jie Hu, Encheng Li, Ming Ding, Rulong Shen, John P. Pineda, Chun Li, Shaohua Lu, Hongyu Yu, Jiayuan Sun, Wenbin Huang, Xiaonan Wang, Han Si, Panying Shi…
    Citation: Clinical Epigenetics 2021 13:220
    Content type: Research Published on:

  25. The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often ...

    Authors: Ashna Maredia, David Guzzardi, Mohammad Aleinati, Fatima Iqbal, Arshroop Khaira, Aiswarya Madhu, Xuemei Wang, Alex J. Barker, Patrick M. McCarthy, Paul W. M. Fedak and Steven C. Greenway
    Citation: Clinical Epigenetics 2021 13:147
    Content type: Research Published on:

  26. Increasing evidence linking epigenetic mechanisms and different diseases, including cancer, has prompted in the last 15 years the investigation of histone post-translational modifications (PTMs) in clinical sa...

    Authors: Roberta Noberini, Evelyn Oliva Savoia, Stefania Brandini, Francesco Greco, Francesca Marra, Giovanni Bertalot, Giancarlo Pruneri, Liam A. McDonnell and Tiziana Bonaldi
    Citation: Clinical Epigenetics 2021 13:145
    Content type: Methodology Published on:

  27. Current risk models for renal cell carcinoma (RCC) based on clinicopathological factors are sub-optimal in accurately identifying high-risk patients. Here, we perform a head-to-head comparison of previously pu...

    Authors: S. C. Joosten, S. N. O. Odeh, A. Koch, N. Buekers, M. J. B. Aarts, M. M. L. L. Baldewijns, L. Van Neste, S. van Kuijk, L. J. Schouten, P. A. van den Brandt, V. C. Tjan-Heijnen, M. van Engeland and K. M. Smits
    Citation: Clinical Epigenetics 2021 13:103
    Content type: Research Published on: