Identical twins carry a persistent epigenetic signature of early genome programming

Jenny van Dongen; Scott D. Gordon; Veronika V. Odintsova; Hamdi Mbarek; Fiona A. Hagenbeek; Catharina E.M. van Beijsterveldt; Jouke Jan Hottenga; Eco J.C. de Geus; Gonneke Willemsen; Dorret I. Boomsma; Genetics of DNA Methylation Consortium; BIOS Consortium

doi:10.1038/s41467-021-25583-7

Identical twins carry a persistent epigenetic signature of early genome programming

Jenny van Dongen, Scott D. Gordon, Veronika V. Odintsova, Hamdi Mbarek, Fiona A. Hagenbeek, Catharina E.M. van Beijsterveldt, Jouke Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Dorret I. Boomsma, Genetics of DNA Methylation Consortium, BIOS Consortium

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 language	English
Article number	5618
Pages (from-to)	1-14
Number of pages	14
Journal	Nature Communications
Volume	12
Early online date	28 Sept 2021
DOIs	https://doi.org/10.1038/s41467-021-25583-7
Publication status	Published - 2021

Bibliographical note

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

Funding

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.

Funders	Funder number
Biobanking and Biomolecular Research Infrastructure
Not added	184.034.019
BBMRI	184.033.111, 184.021.007

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.nature.com/articles/s41467-021-25583-7

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van Dongen, J., Gordon, S. D., Odintsova, V. V., Mbarek, H., Hagenbeek, F. A., van Beijsterveldt, C. E. M., Jan Hottenga, J., de Geus, E. J. C., Willemsen, G., Boomsma, D. I., Genetics of DNA Methylation Consortium, & BIOS Consortium (2021). Identical twins carry a persistent epigenetic signature of early genome programming. Nature Communications, 12, 1-14. Article 5618. https://doi.org/10.1038/s41467-021-25583-7

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title = "Identical twins carry a persistent epigenetic signature of early genome programming",

abstract = "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.",

author = "\{van Dongen\}, Jenny and Gordon, \{Scott D.\} and McRae, \{Allan F.\} and Odintsova, \{Veronika V.\} and Hamdi Mbarek and Breeze, \{Charles E.\} and Karen Sugden and Sara Lundgren and Eilis Hannon and Moffitt, \{Terrie E.\} and Hagenbeek, \{Fiona A.\} and \{van Beijsterveldt\}, \{Catharina E.M.\} and \{Jan Hottenga\}, Jouke and Tsai, \{Pei Chien\} and McRae, \{Allan F.\} and Castillo-Fernandez, \{Juan E.\} and \{de Geus\}, \{Eco J.C.\} and Spector, \{Timothy D.\} and Min, \{Josine L.\} and Gibran Hemani and Ehli, \{Erik A.\} and Franziska Paul and Stern, \{Claudio D.\} and Heijmans, \{Bastiaan T.\} and Slagboom, \{P. Eline\} and Lucia Daxinger and \{van der Maarel\}, \{Silv{\`e}re M.\} and Gonneke Willemsen and Montgomery, \{Grant W.\} and Bruno Reversade and Miina Ollikainen and Jaakko Kaprio and Bell, \{Jordana T.\} and Jonathan Mill and Avshalom Caspi and Martin, \{Nicholas G.\} and Boomsma, \{Dorret I.\} and \{Genetics of DNA Methylation Consortium\} and \{BIOS Consortium\}",

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year = "2021",

doi = "10.1038/s41467-021-25583-7",

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van Dongen, J, Gordon, SD, Odintsova, VV, Mbarek, H, Hagenbeek, FA, van Beijsterveldt, CEM, Jan Hottenga, J , de Geus, EJC, Willemsen, G, Boomsma, DI, Genetics of DNA Methylation Consortium & BIOS Consortium 2021, 'Identical twins carry a persistent epigenetic signature of early genome programming', Nature Communications, vol. 12, 5618, pp. 1-14. https://doi.org/10.1038/s41467-021-25583-7

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T1 - Identical twins carry a persistent epigenetic signature of early genome programming

AU - van Dongen, Jenny

AU - Gordon, Scott D.

AU - McRae, Allan F.

AU - Odintsova, Veronika V.

AU - Mbarek, Hamdi

AU - Breeze, Charles E.

AU - Sugden, Karen

AU - Lundgren, Sara

AU - Hannon, Eilis

AU - Moffitt, Terrie E.

AU - Hagenbeek, Fiona A.

AU - van Beijsterveldt, Catharina E.M.

AU - Jan Hottenga, Jouke

AU - Tsai, Pei Chien

AU - McRae, Allan F.

AU - Castillo-Fernandez, Juan E.

AU - de Geus, Eco J.C.

AU - Spector, Timothy D.

AU - Min, Josine L.

AU - Hemani, Gibran

AU - Ehli, Erik A.

AU - Paul, Franziska

AU - Stern, Claudio D.

AU - Heijmans, Bastiaan T.

AU - Slagboom, P. Eline

AU - Daxinger, Lucia

AU - van der Maarel, Silvère M.

AU - Willemsen, Gonneke

AU - Montgomery, Grant W.

AU - Reversade, Bruno

AU - Ollikainen, Miina

AU - Kaprio, Jaakko

AU - Bell, Jordana T.

AU - Mill, Jonathan

AU - Caspi, Avshalom

AU - Martin, Nicholas G.

AU - Boomsma, Dorret I.

AU - Genetics of DNA Methylation Consortium

AU - BIOS Consortium

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SN - 2041-1723

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EP - 14

JO - Nature Communications

JF - Nature Communications

M1 - 5618

ER -

Identical twins carry a persistent epigenetic signature of early genome programming

Abstract

Bibliographical note

Funding

UN SDGs

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