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

TitleAssociation between perinatal methylation of the neuronal differentiation regulator HES1 and later childhood neurocognitive function and behaviour.
Publication TypeJournal Article
Year of Publication2015
AuthorsLillycrop KA, Costello PM, Teh ALing, Murray RJ, Clarke-Harris R, Barton SJ, Garratt ES, Ngo S, Sheppard AM, Wong J, Dogra S, Burdge GC, Cooper C, Inskip HM, Gale CR, Gluckman PD, Harvey NC, Chong Y-S, Yap F, Meaney MJ, Rifkin-Graboi A, Holbrook JD, Godfrey KM
Corporate AuthorsEpigen Global Research Consortium
JournalInt J Epidemiol
Volume44
Issue4
Pagination1263-76
Date Published2015 Aug
ISSN1464-3685
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 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.

DOI10.1093/ije/dyv052
Alternate JournalInt J Epidemiol
PubMed ID25906782
PubMed Central IDPMC4588869
Grant ListMC_ST_U12055 / / Medical Research Council / United Kingdom
MC_U147585827 / / Medical Research Council / United Kingdom
MC_UP_A620_1014 / / Medical Research Council / United Kingdom
MC_UU_12011/1 / / Medical Research Council / United Kingdom
RG/07/009 / / British Heart Foundation / United Kingdom