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Lookup NU author(s): Professor Caroline Relton
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Gestational age (GA) and birth weight have been implicated in the determination of long-term health. It has been hypothesized that changes in DNA methylation may mediate these long-term effects. We obtained DNA methylation profiles from cord blood and peripheral blood at ages 7 and 17 in the same children from the Avon Longitudinal Study of Parents and Children. Repeated-measures data were used to investigate changes in birth-related methylation during childhood and adolescence. Ten developmental phenotypes (e.g. height) were analysed to identify possible mediation of health effects by DNA methylation. In cord blood, methylation at 224 CpG sites was found to be associated with GA and 23 CpG sites with birth weight. Methylation changed in the majority of these sites over time, but neither birth characteristic was strongly associated with methylation at age 7 or 17 (using a conservative correction for multiple testing of P < 1.03 x 10(-7)), suggesting resolution of differential methylation by early childhood. Associations were observed between birth weight-associated CpG sites and phenotypic characteristics in childhood. One strong association involved birth weight, methylation of a CpG site proximal to the NFIX locus and bone mineral density at age 17. Analysis of serial methylation from birth to adolescence provided evidence for a lack of persistence of methylation differences beyond early childhood. Sites associated with birth weight were linked to developmental genes and have methylation levels which are associated with developmental phenotypes. Replication and interrogation of causal relationships are needed to substantiate whether methylation differences at birth influence the association between birth weight and development.
Author(s): Simpkin AJ, Suderman M, Gaunt TR, Lyttleton O, McArdle WL, Ring SM, Tilling K, Smith GD, Relton CL
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2015
Volume: 24
Issue: 13
Pages: 3752-3763
Print publication date: 01/07/2015
Online publication date: 13/04/2015
Acceptance date: 04/04/2015
Date deposited: 05/04/2016
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddv119
DOI: 10.1093/hmg/ddv119
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