Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles
1 Laboratory of EpiGenetics, FR 8.3 Life Sciences, Saarland University, Saarbrücken, 66123, Saarland, Germany
2 Department of Genetics and Cell Biology, Maastricht University, Maastricht, 6200 MD, Limburg, The Netherlands
3 Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht, 6200 MD, Limburg, The Netherlands
4 Department of Psychiatry and Psychotherapy, Saarland University Hospital, Homburg, 66424, Saarland, Germany
5 Department of Human Genetics, University Hospital Gasthuisberg, Katholieke Universiteit Leuven, Leuven, B-3000, Vlaams-Brabant, Belgium
6 Unit of Urologic and Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, Birmingham, B15 2TT, West Midlands, UK
Genome Biology 2013, 14:R44 doi:10.1186/gb-2013-14-5-r44Published: 26 May 2013
Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes.
Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences.
Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies.