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Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour

Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour
Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour
Background: Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but as yet there is little direct evidence for such mechanisms in humans.

Method: We examined the relation between DNA methylation at birth and child neuropsychological outcomes in two culturally diverse populations using a genome-wide methylation analysis and validation by pyrosequencing.

Results: Within the UK Southampton Women’s Survey (SWS) we first which identified 41 differentially methylated regions of interest (DMROI) at birth associated with child’s full-scale IQ at age 4-years. Associations between HES1 DMROI methylation and later cognitive function were confirmed by pyrosequencing in 175 SWS children. Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS seven-year olds. Finally, we examined a pathway for this relationship within a Singaporean cohort (n=108). Here, HES1 DMROI methylation predicted differences in early infant behavior, known to be associated with academic success. In vitro, methylation of HES1 inhibited ETS transcription factor binding, suggesting a functional role of this site.

Conclusions: Thus, our findings suggest that perinatal epigenetic processes mark later neuro-cognitive function and behavior, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development.
0300-5771
1263–1276
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Costello, Paula M.
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Teh, Ai Ling
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Murray, Robert J.
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Clarke-Harris, Rebecca
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Barton, Sheila J.
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Garratt, Emma S.
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Ngo, Sherry
19990b41-bd2f-45cb-bd34-ae1652d15b96
Sheppard, Alan M.
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Wong, Johnny
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Dogra, Shaillay
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Burdge, Graham C.
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Cooper, Cyrus
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Inskip, Hazel M.
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Gale, Catharine R.
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Gluckman, Peter D.
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Harvey, Nicholas C.
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Chong, Yap-Seng
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Yap, Fabian
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Meaney, Michael J.
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Rifkin-Grabot, Anne
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Holbrook, Joanna
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Godfrey, Keith M.
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Epigen Global Research Consortium
Lillycrop, Karen A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Costello, Paula M.
8fc5c643-2d38-4443-975a-8704af2fa755
Teh, Ai Ling
af437ef4-60d8-4b1f-9c3c-54ab35a1ac23
Murray, Robert J.
c3e973b5-525c-49b3-96ee-af60a666a0f4
Clarke-Harris, Rebecca
7fc6eb8b-28cb-48cf-926f-84a9fd05b363
Barton, Sheila J.
4f674382-ca0b-44ad-9670-e71a0b134ef0
Garratt, Emma S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Ngo, Sherry
19990b41-bd2f-45cb-bd34-ae1652d15b96
Sheppard, Alan M.
4e8a2c02-b442-41d7-a246-86d898dd8ce4
Wong, Johnny
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Dogra, Shaillay
5b21d189-6557-416a-bebc-46c21f01e8c4
Burdge, Graham C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Cooper, Cyrus
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Inskip, Hazel M.
5fb4470a-9379-49b2-a533-9da8e61058b7
Gale, Catharine R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Gluckman, Peter D.
ef2e8b92-0b76-4a12-bd7c-01b0674f94d3
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Chong, Yap-Seng
920e715b-2dfb-4ae7-ae9c-59c50513ffaf
Yap, Fabian
84f36f12-193e-44c8-80f9-b342241eb72f
Meaney, Michael J.
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Rifkin-Grabot, Anne
4a596bf9-2197-476f-bc11-dd78436dd281
Holbrook, Joanna
69989b79-2710-4f12-946e-c6214e1b6513
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd

Lillycrop, Karen A., Costello, Paula M., Teh, Ai Ling, Murray, Robert J., Clarke-Harris, Rebecca, Barton, Sheila J., Garratt, Emma S., Ngo, Sherry, Sheppard, Alan M., Wong, Johnny, Dogra, Shaillay, Burdge, Graham C., Cooper, Cyrus, Inskip, Hazel M., Gale, Catharine R., Gluckman, Peter D., Harvey, Nicholas C., Chong, Yap-Seng, Yap, Fabian, Meaney, Michael J., Rifkin-Grabot, Anne, Holbrook, Joanna and Godfrey, Keith M. , Epigen Global Research Consortium (2015) Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour. International Journal of Epidemiology, 44 (4), 1263–1276. (doi:10.1093/ije/dyv052). (PMID:25906782)

Record type: Article

Abstract

Background: Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but as yet there is little direct evidence for such mechanisms in humans.

Method: We examined the relation between DNA methylation at birth and child neuropsychological outcomes in two culturally diverse populations using a genome-wide methylation analysis and validation by pyrosequencing.

Results: Within the UK Southampton Women’s Survey (SWS) we first which identified 41 differentially methylated regions of interest (DMROI) at birth associated with child’s full-scale IQ at age 4-years. Associations between HES1 DMROI methylation and later cognitive function were confirmed by pyrosequencing in 175 SWS children. Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS seven-year olds. Finally, we examined a pathway for this relationship within a Singaporean cohort (n=108). Here, HES1 DMROI methylation predicted differences in early infant behavior, known to be associated with academic success. In vitro, methylation of HES1 inhibited ETS transcription factor binding, suggesting a functional role of this site.

Conclusions: Thus, our findings suggest that perinatal epigenetic processes mark later neuro-cognitive function and behavior, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development.

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Accepted/In Press date: 2015
e-pub ahead of print date: 22 April 2015
Published date: August 2015
Organisations: Biomedicine

Identifiers

Local EPrints ID: 377452
URI: https://eprints.soton.ac.uk/id/eprint/377452
ISSN: 0300-5771
PURE UUID: ad89855b-b2f1-431c-903d-3382e139e92e
ORCID for Karen A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Rebecca Clarke-Harris: ORCID iD orcid.org/0000-0002-6888-9518
ORCID for Sheila J. Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Emma S. Garratt: ORCID iD orcid.org/0000-0001-5268-4203
ORCID for Graham C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Hazel M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Catharine R. Gale: ORCID iD orcid.org/0000-0002-3361-8638
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Joanna Holbrook: ORCID iD orcid.org/0000-0003-1791-6894
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

Catalogue record

Date deposited: 08 Jun 2015 10:20
Last modified: 20 Jul 2019 06:06

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Contributors

Author: Paula M. Costello
Author: Ai Ling Teh
Author: Robert J. Murray
Author: Rebecca Clarke-Harris ORCID iD
Author: Emma S. Garratt ORCID iD
Author: Sherry Ngo
Author: Alan M. Sheppard
Author: Johnny Wong
Author: Shaillay Dogra
Author: Cyrus Cooper ORCID iD
Author: Hazel M. Inskip ORCID iD
Author: Peter D. Gluckman
Author: Yap-Seng Chong
Author: Fabian Yap
Author: Michael J. Meaney
Author: Anne Rifkin-Grabot
Author: Joanna Holbrook ORCID iD

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