Identical twins carry a persistent epigenetic signature of early genome programming

Research output: Contribution to JournalArticleAcademicpeer-review


Monozygotic (MZ) twins and higher-order multiples arise when a zygote splits during pre-implantation stages of development. The mechanisms underpinning this event have remained a mystery. Because MZ twinning rarely runs in families, the leading hypothesis is that it occurs at random. Here, we show that MZ twinning is strongly associated with a stable DNA methylation signature in adult somatic tissues. This signature spans regions near telomeres and centromeres, Polycomb-repressed regions and heterochromatin, genes involved in cell-adhesion, WNT signaling, cell fate, and putative human metastable epialleles. Our study also demonstrates a never-anticipated corollary: because identical twins keep a lifelong molecular signature, we can retrospectively diagnose if a person was conceived as monozygotic twin.

Original languageEnglish
Article number5618
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 28 Sep 2021

Bibliographical note

Funding Information:
We acknowledge funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111), and NWO Large Scale infrastructures, X-Omics (184.034.019). Cohort-specific acknowledgments are provided in Supplementary Note 8. We thank Peter Visscher and Jian Yang for their helpful comments.

Publisher Copyright:
© 2021, The Author(s).

Cohort Studies

  • Netherlands Twin Register (NTR)


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