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Type: Journal article
Title: 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
Author: Sharp, G.
Lawlor, D.
Richmond, R.
Fraser, A.
Simpkin, A.
Suderman, M.
Shihab, H.
Lyttleton, O.
McArdle, W.
Ring, S.
Gaunt, T.
Smith, G.
Relton, C.
Citation: International Journal of Epidemiology, 2015; 44(4):1288-1304
Publisher: Oxford University Press
Issue Date: 2015
ISSN: 0300-5771
Statement of
Gemma C Sharp, Debbie A Lawlor, Rebecca C Richmond, Abigail Fraser, Andrew Simpkin, Matthew Suderman, Hashem A Shihab, Oliver Lyttleton, Wendy McArdle, Susan M Ring, Tom R Gaunt, George Davey Smith and Caroline L Relton
Abstract: 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.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.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.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.
Keywords: Epigenetic; ALSPAC; ARIES; causality; epigenome-wide; association study; longitudinal; overweight; overnutritin; undernutrition
Rights: © The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association 1288 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
DOI: 10.1093/ije/dyv042
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