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

Autor:	Lillycrop KA; Centre for Biological Sciences, and NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK, kal@soton.ac.uk., Costello PM; Academic Unit of Human Development and Health, University of Southampton, Southampton, UK., Teh AL; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore., Murray RJ; Academic Unit of Human Development and Health, University of Southampton, Southampton, UK., Clarke-Harris R; Academic Unit of Human Development and Health, University of Southampton, Southampton, UK., Barton SJ; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Garratt ES; Academic Unit of Human Development and Health, University of Southampton, Southampton, UK., Ngo S; Liggins Institute, University of Auckland, Auckland, New Zealand., Sheppard AM; Liggins Institute, University of Auckland, Auckland, New Zealand., Wong J; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore., Dogra S; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore., Burdge GC; Academic Unit of Human Development and Health, University of Southampton, Southampton, UK., Cooper C; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK, NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK., Inskip HM; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Gale CR; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK., Gluckman PD; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Liggins Institute, University of Auckland, Auckland, New Zealand., Harvey NC; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK., Chong YS; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Yap F; Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Duke NUS Graduate School of Medicine, National University of Singapore, Singapore, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore and., Meaney MJ; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montréal, Canada., Rifkin-Graboi A; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore., Holbrook JD; Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore., Godfrey KM; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK, NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.
Jazyk:	angličtina
Zdroj:	International journal of epidemiology [Int J Epidemiol] 2015 Aug; Vol. 44 (4), pp. 1263-76. Date of Electronic Publication: 2015 Apr 22.
DOI:	10.1093/ije/dyv052
Abstrakt:	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. (© The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.)
Databáze:	MEDLINE
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