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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 exam...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588869/ https://www.ncbi.nlm.nih.gov/pubmed/25906782 http://dx.doi.org/10.1093/ije/dyv052 |
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author | Lillycrop, Karen A Costello, Paula M Teh, Ai Ling Murray, Robert J Clarke-Harris, Rebecca Barton, Sheila J Garratt, Emma S Ngo, Sherry Sheppard, Allan 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-Graboi, Anne Holbrook, Joanna D Godfrey, Keith M |
author_facet | Lillycrop, Karen A Costello, Paula M Teh, Ai Ling Murray, Robert J Clarke-Harris, Rebecca Barton, Sheila J Garratt, Emma S Ngo, Sherry Sheppard, Allan 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-Graboi, Anne Holbrook, Joanna D Godfrey, Keith M |
author_sort | Lillycrop, Karen A |
collection | PubMed |
description | 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 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 7-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 behaviour, 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 neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development. |
format | Online Article Text |
id | pubmed-4588869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-45888692015-10-01 Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour Lillycrop, Karen A Costello, Paula M Teh, Ai Ling Murray, Robert J Clarke-Harris, Rebecca Barton, Sheila J Garratt, Emma S Ngo, Sherry Sheppard, Allan 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-Graboi, Anne Holbrook, Joanna D Godfrey, Keith M Int J Epidemiol Early Life Environment 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 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 7-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 behaviour, 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 neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development. Oxford University Press 2015-08 2015-04-22 /pmc/articles/PMC4588869/ /pubmed/25906782 http://dx.doi.org/10.1093/ije/dyv052 Text en © The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Early Life Environment Lillycrop, Karen A Costello, Paula M Teh, Ai Ling Murray, Robert J Clarke-Harris, Rebecca Barton, Sheila J Garratt, Emma S Ngo, Sherry Sheppard, Allan 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-Graboi, Anne Holbrook, Joanna D Godfrey, Keith M Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title | Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title_full | Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title_fullStr | Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title_full_unstemmed | Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title_short | Association between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour |
title_sort | association between perinatal methylation of the neuronal differentiation regulator hes1 and later childhood neurocognitive function and behaviour |
topic | Early Life Environment |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588869/ https://www.ncbi.nlm.nih.gov/pubmed/25906782 http://dx.doi.org/10.1093/ije/dyv052 |
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