Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance
- Equal contributors
1 Cancer, Disease and Developmental Epigenetics, Murdoch Childrens Research Institute (MCRI), Flemington Road, Parkville, Victoria 3052, Australia
2 Early Life Epigenetics Group, MCRI, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
3 Department of Paediatrics University of Melbourne, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
4 Bioinformatics Unit, MCRI, Royal Children's Hospital, Flemington Road, Parkville, Victoria 3052, Australia
5 Hjelt Institute, Department of Public Health, University of Helsinki, Mannerheimintie 172, 00300 Helsinki, Finland
6 Current address: Division of Leukaemia and Cancer Research, Telethon Institute for Child Health Research, Centre for Child Health, University of Western Australia, 100 Roberts Road, Subiaco, Western Australia 6008, Australia
Genome Biology 2013, 14:R42 doi:10.1186/gb-2013-14-5-r42Published: 22 May 2013
The extent to which development- and age-associated epigenetic changes are influenced by genetic, environmental and stochastic factors remains to be discovered. Twins provide an ideal model with which to investigate these influences but previous cross-sectional twin studies provide contradictory evidence of within-pair epigenetic drift over time. Longitudinal twin studies can potentially address this discrepancy.
In a pilot, genome-scale study of DNA from buccal epithelium, a relatively homogeneous tissue, we show that one-third of the CpGs assayed show dynamic methylation between birth and 18 months. Although all classes of annotated genomic regions assessed show an increase in DNA methylation over time, probes located in intragenic regions, enhancers and low-density CpG promoters are significantly over-represented, while CpG islands and high-CpG density promoters are depleted among the most dynamic probes. Comparison of co-twins demonstrated that within-pair drift in DNA methylation in our cohort is specific to a subset of pairs, who show more differences at 18 months. The rest of the pairs show either minimal change in methylation discordance, or more similar, converging methylation profiles at 18 months. As with age-associated regions, sites that change in their level of within-pair discordance between birth and 18 months are enriched in genes involved in development, but the average magnitude of change is smaller than for longitudinal change.
Our findings suggest that DNA methylation in buccal epithelium is influenced by non-shared stochastic and environmental factors that could reflect a degree of epigenetic plasticity within an otherwise constrained developmental program.