Identical twins carry a persistent epigenetic signature of early genome programming

Dongen, J. van; Gordon, S.D.; McRae, A.F.; Odintsova, V.V.; Mbarek, H.; Breeze, C.E.; Sugden, K.; Lundgren, S.; Castillo-Fernandez, J.E.; Hannon, E.; Moffitt, T.E.; Hagenbeek, F.A.; Beijsterveldt, C.E.M. van; Hottenga, J.J.; Tsai, P.C.; Min, J.L.; Hemani, G.; Ehli, E.A.; Paul, F.; Stern, C.D.; Heijmans, B.T.; Slagboom, P.E.; Daxinger, L.; Maarel, S.M. van der; Geus, E.J.C. de; Willemsen, G.; Montgomery, G.W.; Reversade, B.; Ollikainen, M.; Kaprio, J.; Spector, T.D.; Bell, J.T.; Mill, J.; Caspi, A.; Martin, N.G.; Boomsma, D.I.; Bios Consortium; Genetics DNA Methylation Consortiu

doi:doi:10.1038/s41467-021-25583-7

The mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues.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...Show moreThe mechanisms underlying how monozygotic (or identical) twins arise are yet to be determined. Here, the authors investigate this in an epigenome-wide association study, showing that monozygotic twinning has a characteristic DNA methylation signature in adult somatic tissues.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.Show less

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Identical twins carry a persistent epigenetic signature of early genome programming