Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

N.Y.P. Souren, P. Lutsik, G. Gasparoni, S. Tierling, J. Gries, M. Riemenschneider, J.P. Frijns, C. Derom, M.P.A. Zeegers, J. Walter

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BACKGROUND: 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. RESULTS: 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 3153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean beta-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remained 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. CONCLUSIONS: 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.
Original languageEnglish
Article number44
Number of pages15
JournalGenome Biology
Issue number5
Publication statusPublished - 1 Jan 2013


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Souren, N. Y. P., Lutsik, P., Gasparoni, G., Tierling, S., Gries, J., Riemenschneider, M., Frijns, J. P., Derom, C., Zeegers, M. P. A., & Walter, J. (2013). Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles. Genome Biology, 14(5), [44].