| Title: |
O-210 DNA methylation signature of monozygotic twinning: investigating the relationship with medically assisted reproduction, higher-order gestations, and common genetic variants |
| Authors: |
Van Dongen, J; Odintsova, V; Hubers, N; GoDMC, T; Hagenbeek, F; Ehli, E; Hottenga, J J; De Bakker, B; Henneman, P; Ris-Stalpers, C; Boomsma, D |
| Source: |
Human Reproduction ; volume 39, issue Supplement_1 ; ISSN 0268-1161 1460-2350 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
Study question To study a DNA methylation signature of monozygotic twins in relation to medically assisted reproduction (MAR), higher-order gestations, and genome-wide common genetic variants. Summary answer Monozygotic twinning and MAR show largely distinct DNA methylation signatures. Monozygotic triplets, like monozygotic twins, carry a comparable but stronger DNA methylation signature. What is known already Monozygotic twins arise when a zygote or embryo splits during pre-implantation stages of development. Higher-order monozygotic multiples including triplets have been hypothesized to arise from multiple consecutive splitting events. The underlying mechanisms are unknown. Some studies have reported a higher rate of monozygotic twins born after the use of medically-assisted reproductive technologies. We recently identified a DNA methylation signature in blood samples from adult monozygotic twins, which showed strong replication across cohorts and in buccal samples from children. This signature consists of 834 differentially methylated locations, enriched for loci with a role in embryonic processes, cell adhesion, and metastable epi-alleles. Study design, size, duration We compared buccal DNA methylation profiles of 934 naturally conceived monozygotic twins to 43 monozygotic twins conceived after IVF/ICSI (mean age=9). We generated monozygotic twinning DNA methylation scores in an independent buccal dataset (59 triplets, 198 twins, and 119 siblings of twins, mean age=15). A genome-wide association study (GWAS) on the DNA methylation score was performed in two datasets from the Netherlands Twin Register (NTR) (1: Blood, N = 2841, mean age=37, 2: Buccal, N = 1150, mean age=10). Participants/materials, setting, methods DNA methylation was assessed with Illumina arrays (450k/EPIC). To study the relationship between DNA methylation and MAR, we performed an epigenome-wide association study (EWAS) of MAR in monozygotic twins. We applied our previously developed DNA-methylation based predictor (trained on ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/humrep/deae108.243 |
| Availability: |
https://doi.org/10.1093/humrep/deae108.243; https://academic.oup.com/humrep/article-pdf/39/Supplement_1/deae108.243/58509669/deae108.243.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.3DC3DF8E |
| Database: |
BASE |