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Maternal pre-pregnancy BMI and gestational weight gain, offspring DNA methylation and later offspring adiposity: findings from the Avon Longitudinal Study of Parents and Children

Lookup NU author(s): Professor Caroline Relton

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Background: Evidence suggests that in utero exposure to undernutrition and overnutrition might affect adiposity in later life. Epigenetic modification is suggested as a plausible mediating mechanism.Methods: We used multivariable linear regression and a negative control design to examine offspring epigenome-wide DNA methylation in relation to maternal and offspring adiposity in 1018 participants.Results: Compared with neonatal offspring of normal weight mothers, 28 and 1621 CpG sites were differentially methylated in offspring of obese and underweight mothers, respectively [false discovert rate (FDR)-corrected P-value<0.05), with no overlap in the sites that maternal obesity and underweight relate to. A positive association, where higher methylation is associated with a body mass index (BMI) outside the normal range, was seen at 78.6% of the sites associated with obesity and 87.9% of the sites associated with underweight. Associations of maternal obesity with offspring methylation were stronger than associations of paternal obesity, supporting an intrauterine mechanism. There were no consistent associations of gestational weight gain with offspring DNA methylation. In general, sites that were hypermethylated in association with maternal obesity or hypomethylated in association with maternal underweight tended to be positively associated with offspring adiposity, and sites hypomethylated in association with maternal obesity or hypermethylated in association with maternal underweight tended to be inversely associated with offspring adiposity.Conclusions: Our data suggest that both maternal obesity and, to a larger degree, underweight affect the neonatal epigenome via an intrauterine mechanism, but weight gain during pregnancy has little effect. We found some evidence that associations of maternal underweight with lower offspring adiposity and maternal obesity with greater offspring adiposity may be mediated via increased DNA methylation.


Publication metadata

Author(s): Sharp GC, Lawlor DA, Richmond RC, Fraser A, Simpkin A, Suderman M, Shihab HA, Lyttleton O, McArdle W, Ring SM, Gaunt TR, Smith GD, Relton CL

Publication type: Article

Publication status: Published

Journal: International Journal of Epidemiology

Year: 2015

Volume: 44

Issue: 4

Pages: 1288-1304

Print publication date: 01/08/2015

Online publication date: 08/04/2015

Acceptance date: 10/03/2015

Date deposited: 05/04/2016

ISSN (print): 0300-5771

ISSN (electronic): 1464-3685

Publisher: Oxford University Press

URL: http://dx.doi.org/10.1093/ije/dyv042

DOI: 10.1093/ije/dyv042


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Funding

Funder referenceFunder name
MRC Integrative Epidemiology Unit
0701594/1UK Medical Research Council
102215/2/13/2Wellcome Trust
269874European Research Council grant DEVHEALTH
BB/I025751/1UK Biotechnology and Biological Sciences Research Council
BB/I025263/1UK Biotechnology and Biological Sciences Research Council
MC_UU_12013_8University of Bristol
MC_UU_12013_2University of Bristol
MC_UU_12013_5University of Bristol
RES-060-23-0011ESRC
R01 DK10324United States National Institute of Diabetes and Digestive and Kidney Diseases
WT083431MFWellcome Trust
WT094529MAWellcome Trust

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