Epigenetic supersimilarity of monozygotic twin pairs

Timothy E. van Baak, Cristian Coarfa, Pierre Antoine Dugué, Giovanni Fiorito, Eleonora Laritsky, Maria S. Baker, Noah J. Kessler, Jianrong Dong, Jack D. Duryea, Matt J. Silver, Ayden Saffari, Andrew M. Prentice, Sophie E. Moore, Akram Ghantous, Michael N. Routledge, Yun Yun Gong, Zdenko Herceg, Paolo Vineis, Gianluca Severi, John L. Hopper & 4 others Melissa C. Southey, Graham G. Giles, Roger L. Milne, Robert A. Waterland

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Results: Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer. Conclusions: These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.

Original languageEnglish
Article number2
Number of pages20
JournalGenome Biology
Volume19
Issue number1
DOIs
Publication statusPublished - 9 Jan 2018
Externally publishedYes

Keywords

  • Cancer
  • Developmental programming
  • Dizygotic
  • DOHaD
  • Epigenetics
  • Metastable epialleles
  • Monozygotic
  • Twins

Cite this

van Baak, T. E., Coarfa, C., Dugué, P. A., Fiorito, G., Laritsky, E., Baker, M. S., ... Waterland, R. A. (2018). Epigenetic supersimilarity of monozygotic twin pairs. Genome Biology, 19(1), [2]. https://doi.org/10.1186/s13059-017-1374-0
van Baak, Timothy E. ; Coarfa, Cristian ; Dugué, Pierre Antoine ; Fiorito, Giovanni ; Laritsky, Eleonora ; Baker, Maria S. ; Kessler, Noah J. ; Dong, Jianrong ; Duryea, Jack D. ; Silver, Matt J. ; Saffari, Ayden ; Prentice, Andrew M. ; Moore, Sophie E. ; Ghantous, Akram ; Routledge, Michael N. ; Gong, Yun Yun ; Herceg, Zdenko ; Vineis, Paolo ; Severi, Gianluca ; Hopper, John L. ; Southey, Melissa C. ; Giles, Graham G. ; Milne, Roger L. ; Waterland, Robert A. / Epigenetic supersimilarity of monozygotic twin pairs. In: Genome Biology. 2018 ; Vol. 19, No. 1.
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van Baak, TE, Coarfa, C, Dugué, PA, Fiorito, G, Laritsky, E, Baker, MS, Kessler, NJ, Dong, J, Duryea, JD, Silver, MJ, Saffari, A, Prentice, AM, Moore, SE, Ghantous, A, Routledge, MN, Gong, YY, Herceg, Z, Vineis, P, Severi, G, Hopper, JL, Southey, MC, Giles, GG, Milne, RL & Waterland, RA 2018, 'Epigenetic supersimilarity of monozygotic twin pairs' Genome Biology, vol. 19, no. 1, 2. https://doi.org/10.1186/s13059-017-1374-0

Epigenetic supersimilarity of monozygotic twin pairs. / van Baak, Timothy E.; Coarfa, Cristian; Dugué, Pierre Antoine; Fiorito, Giovanni; Laritsky, Eleonora; Baker, Maria S.; Kessler, Noah J.; Dong, Jianrong; Duryea, Jack D.; Silver, Matt J.; Saffari, Ayden; Prentice, Andrew M.; Moore, Sophie E.; Ghantous, Akram; Routledge, Michael N.; Gong, Yun Yun; Herceg, Zdenko; Vineis, Paolo; Severi, Gianluca; Hopper, John L.; Southey, Melissa C.; Giles, Graham G.; Milne, Roger L.; Waterland, Robert A.

In: Genome Biology, Vol. 19, No. 1, 2, 09.01.2018.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Epigenetic supersimilarity of monozygotic twin pairs

AU - van Baak, Timothy E.

AU - Coarfa, Cristian

AU - Dugué, Pierre Antoine

AU - Fiorito, Giovanni

AU - Laritsky, Eleonora

AU - Baker, Maria S.

AU - Kessler, Noah J.

AU - Dong, Jianrong

AU - Duryea, Jack D.

AU - Silver, Matt J.

AU - Saffari, Ayden

AU - Prentice, Andrew M.

AU - Moore, Sophie E.

AU - Ghantous, Akram

AU - Routledge, Michael N.

AU - Gong, Yun Yun

AU - Herceg, Zdenko

AU - Vineis, Paolo

AU - Severi, Gianluca

AU - Hopper, John L.

AU - Southey, Melissa C.

AU - Giles, Graham G.

AU - Milne, Roger L.

AU - Waterland, Robert A.

PY - 2018/1/9

Y1 - 2018/1/9

N2 - Background: Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Results: Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer. Conclusions: These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.

AB - Background: Monozygotic twins have long been studied to estimate heritability and explore epigenetic influences on phenotypic variation. The phenotypic and epigenetic similarities of monozygotic twins have been assumed to be largely due to their genetic identity. Results: Here, by analyzing data from a genome-scale study of DNA methylation in monozygotic and dizygotic twins, we identified genomic regions at which the epigenetic similarity of monozygotic twins is substantially greater than can be explained by their genetic identity. This "epigenetic supersimilarity" apparently results from locus-specific establishment of epigenotype prior to embryo cleavage during twinning. Epigenetically supersimilar loci exhibit systemic interindividual epigenetic variation and plasticity to periconceptional environment and are enriched in sub-telomeric regions. In case-control studies nested in a prospective cohort, blood DNA methylation at these loci years before diagnosis is associated with risk of developing several types of cancer. Conclusions: These results establish a link between early embryonic epigenetic development and adult disease. More broadly, epigenetic supersimilarity is a previously unrecognized phenomenon that may contribute to the phenotypic similarity of monozygotic twins.

KW - Cancer

KW - Developmental programming

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KW - Twins

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van Baak TE, Coarfa C, Dugué PA, Fiorito G, Laritsky E, Baker MS et al. Epigenetic supersimilarity of monozygotic twin pairs. Genome Biology. 2018 Jan 9;19(1). 2. https://doi.org/10.1186/s13059-017-1374-0