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DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis

Author

Listed:
  • Nicole Y. Souren

    (Saarland University)

  • Lisa A. Gerdes

    (Ludwig-Maximilians University Munich)

  • Pavlo Lutsik

    (German Cancer Research Center (DKFZ))

  • Gilles Gasparoni

    (Saarland University)

  • Eduardo Beltrán

    (Ludwig-Maximilians University Munich)

  • Abdulrahman Salhab

    (Saarland University)

  • Tania Kümpfel

    (Ludwig-Maximilians University Munich)

  • Dieter Weichenhan

    (German Cancer Research Center (DKFZ))

  • Christoph Plass

    (German Cancer Research Center (DKFZ))

  • Reinhard Hohlfeld

    (Ludwig-Maximilians University Munich
    Munich Cluster for Systems Neurology (SyNergy))

  • Jörn Walter

    (Saarland University)

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with a modest concordance rate in monozygotic twins, which strongly argues for involvement of epigenetic factors. We observe highly similar peripheral blood mononuclear cell-based methylomes in 45 MS-discordant monozygotic twins. Nevertheless, we identify seven MS-associated differentially methylated positions (DMPs) of which we validate two, including a region in the TMEM232 promoter and ZBTB16 enhancer. In CD4 + T cells we find an MS-associated differentially methylated region in FIRRE. Additionally, 45 regions show large methylation differences in individual pairs, but they do not clearly associate with MS. Furthermore, we present epigenetic biomarkers for current interferon-beta treatment, and extensive validation shows that the ZBTB16 DMP is a signature for prior glucocorticoid treatment. Taken together, this study represents an important reference for epigenomic MS studies, identifies new candidate epigenetic markers, and highlights treatment effects and genetic background as major confounders.

Suggested Citation

  • Nicole Y. Souren & Lisa A. Gerdes & Pavlo Lutsik & Gilles Gasparoni & Eduardo Beltrán & Abdulrahman Salhab & Tania Kümpfel & Dieter Weichenhan & Christoph Plass & Reinhard Hohlfeld & Jörn Walter, 2019. "DNA methylation signatures of monozygotic twins clinically discordant for multiple sclerosis," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09984-3
    DOI: 10.1038/s41467-019-09984-3
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    Cited by:

    1. Javier Rodríguez-Ubreva & Anna Arutyunyan & Marc Jan Bonder & Lucía Del Pino-Molina & Stephen J. Clark & Carlos de la Calle-Fabregat & Luz Garcia-Alonso & Louis-François Handfield & Laura Ciudad & Edu, 2022. "Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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