Identical twins carry a persistent epigenetic signature of early genome programming
Jenny van Dongen, Scott D. Gordon, Allan F. McRae, Veronika V. Odintsova, Hamdi Mbarek, Charles E. Breeze, Karen Sugden, Sara Lundgren, Juan Castillo‐Fernandez, Eilís Hannon, Terrie E. Moffitt, Fiona A. Hagenbeek, Catharina E. M. van Beijsterveldt, Jouke‐Jan Hottenga, Pei-Chien Tsai, Jenny van Dongen, Jouke‐Jan Hottenga, Allan F. McRae, Karen Sugden, Juan Castillo‐Fernandez, Eilís Hannon, Terrie E. Moffitt, Jouke‐Jan Hottenga, Eco J. C. de Geus, Timothy D. Spector, Josine L. Min, Gibran Hemani, Erik A. Ehli, Franziska Paul, Claudio D. Stern, Bastiaan T. Heijmans, P. Eline Slagboom, Lucia Daxinger, Silvère M. van der Maarel, Eco J. C. de Geus, Gonneke Willemsen, Grant W. Montgomery, Bruno Reversade, Miina Ollikainen, Jaakko Kaprio, Tim D. Spector, Jordana T. Bell, Jonathan Mill, Avshalom Caspi, Nicholas G. Martin, Dorret I. Boomsma
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.