Examining the Vanishing Twin Hypothesis of Neural Tube Defects: Application of an Epigenetic Predictor for Monozygotic Twinning

Jenny van Dongen; Scott D. Gordon; Veronika V. Odintsova; Allan F. McRae; Wendy P. Robinson; Judith G. Hall; Dorret I. Boomsma; Nicholas G. Martin

doi:10.1017/thg.2021.25

Examining the Vanishing Twin Hypothesis of Neural Tube Defects: Application of an Epigenetic Predictor for Monozygotic Twinning

Jenny van Dongen^*, Scott D. Gordon, Veronika V. Odintsova, Allan F. McRae, Wendy P. Robinson, Judith G. Hall, Dorret I. Boomsma, Nicholas G. Martin

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

Original language	English
Pages (from-to)	155-159
Number of pages	5
Journal	Twin Research and Human Genetics
Volume	24
Issue number	3
DOIs	https://doi.org/10.1017/thg.2021.25
Publication status	Published - Jun 2021

Bibliographical note

Funding Information:
For the Netherlands Twin Register (NTR) epigenetic data, we acknowledge funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111); NTR epigenetic data were generated at the Human Genomics Facility (HuGe-F) at Erasmus Medical Center Rotterdam. JvD is supported by NWO Large Scale infrastructures, X-Omics (184.034.019). DIB acknowledges the Royal Netherlands Academy of Science Professor Award (PAH/6635). The NTD data set (GEO; accession number GSE69502) was supported by a grant to WPR from the Canadian Institutes of Health Research (FRN106430). Collection of Australian twin samples was funded by NHMRC grants to NGM. Australian methylation data were funded by an NHMRC grant to AM.

Publisher Copyright:
© 2021 Cambridge University Press. All rights reserved.

Funding

For the Netherlands Twin Register (NTR) epigenetic data, we acknowledge funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI\u2013NL, 184.021.007; 184.033.111); NTR epigenetic data were generated at the Human Genomics Facility (HuGe-F) at Erasmus Medical Center Rotterdam. JvD is supported by NWO Large Scale infrastructures, X-Omics (184.034.019). DIB acknowledges the Royal Netherlands Academy of Science Professor Award (PAH/6635). The NTD data set (GEO; accession number GSE69502) was supported by a grant to WPR from the Canadian Institutes of Health Research (FRN106430). Collection of Australian twin samples was funded by NHMRC grants to NGM. Australian methylation data were funded by an NHMRC grant to AM.

Funders	Funder number
Biobanking and Biomolecular Research Infrastructure
National Health and Medical Research Council
Not added	184.034.019
Canadian Institutes of Health Research	FRN106430
BBMRI	184.033.111, 184.021.007
Royal Netherlands Academy of Science	GSE69502, PAH/6635

Keywords

anencephaly
DNA methylation
epigenetic
monozygotic twins
Neural tube defects
spina bifida

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1017/thg.2021.25

https://www.cambridge.org/core/product/identifier/S1832427421000256/type/journal_article

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Cite this

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title = "Examining the Vanishing Twin Hypothesis of Neural Tube Defects: Application of an Epigenetic Predictor for Monozygotic Twinning",

abstract = "Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.",

keywords = "anencephaly, DNA methylation, epigenetic, monozygotic twins, Neural tube defects, spina bifida",

author = "{van Dongen}, Jenny and Gordon, {Scott D.} and Odintsova, {Veronika V.} and McRae, {Allan F.} and Robinson, {Wendy P.} and Hall, {Judith G.} and Boomsma, {Dorret I.} and Martin, {Nicholas G.}",

note = "Funding Information: For the Netherlands Twin Register (NTR) epigenetic data, we acknowledge funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI–NL, 184.021.007; 184.033.111); NTR epigenetic data were generated at the Human Genomics Facility (HuGe-F) at Erasmus Medical Center Rotterdam. JvD is supported by NWO Large Scale infrastructures, X-Omics (184.034.019). DIB acknowledges the Royal Netherlands Academy of Science Professor Award (PAH/6635). The NTD data set (GEO; accession number GSE69502) was supported by a grant to WPR from the Canadian Institutes of Health Research (FRN106430). Collection of Australian twin samples was funded by NHMRC grants to NGM. Australian methylation data were funded by an NHMRC grant to AM. Publisher Copyright: {\textcopyright} 2021 Cambridge University Press. All rights reserved.",

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AU - Odintsova, Veronika V.

AU - McRae, Allan F.

AU - Robinson, Wendy P.

AU - Hall, Judith G.

AU - Boomsma, Dorret I.

AU - Martin, Nicholas G.

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N2 - Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

AB - Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

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ER -

Examining the Vanishing Twin Hypothesis of Neural Tube Defects: Application of an Epigenetic Predictor for Monozygotic Twinning

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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