New insights into the (epi)genetics of twinning

Spontaneous dizygotic (DZ) twins, i.e. twins conceived without the use of ARTs, run in families and their prevalence varies widely around the globe. In contrast, monozygotic (MZ) twins occur at a constant rate across time and geographical regions and, with some rare exceptions, do not cluster in families. The leading hypothesis for MZ twins, which arise when a zygote splits during preimplantation stages of development, is random occurrence. We have found the first series of genes underlying the liability of being the mother of DZ twins and have shown that being an MZ twin is strongly associated with a stable DNA methylation signature in child and adult somatic tissues. Because identical twins keep this molecular signature across the lifespan, this discovery opens up completely new possibilities for the retrospective diagnosis of whether a person is an MZ twin whose co-twin may have vanished in the early stages of pregnancy. Here, we summarize the gene finding results for mothers of DZ twins based on genetic association studies followed by meta-analysis, and further present the striking epigenetic results for MZ twins. Graphical Abstract Recent findings regarding the genetic susceptibility to being the mother of dizygotic (DZ) twins (top) and an epigenetic signature associated with being a monozygotic (MZ) twin (bottom). TGC (logo): Twinning Genetics Consortium; SNP: single-nucleotide polymorphism.

Automated summary

The study has identified genes that contribute to the likelihood of a woman giving birth to dizygotic (DZ) twins and has shown that monozygotic (MZ) twins have a stable DNA methylation pattern in their somatic tissues. This discovery opens up new possibilities for retrospective diagnosis of MZ twins and their vanished co-twins in early pregnancy.