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Epigenetic gene promoter methylation at birth is associated with childrens later adiposity

Godfrey, Keith M., Sheppard, Alan, Gluckman, Peter D., Lillycrop, Karen A., Burdge, Graham C., McClean, Cameron, Rodford, Joanne, Slater-Jefferies, Joanne L., Garratt, Emma, Crozier, Sarah R., Emerald, B. Starling, Gale, Catharine R., Inskip, Hazel M., Cooper, Cyrus and Hanson, Mark A. (2011) Epigenetic gene promoter methylation at birth is associated with childrens later adiposity Diabetes, 60, (5), pp. 1528-1534. (PMID:21471513).

Record type: Article


Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.

Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.

Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).

Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic disease

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e-pub ahead of print date: 6 April 2011
Published date: May 2011
Organisations: Human Development & Health, Centre for Biological Sciences


Local EPrints ID: 337148
ISSN: 0012-1797
PURE UUID: a35ba0af-5a90-470b-b1e7-aeb87df55947
ORCID for Keith M. Godfrey: ORCID iD
ORCID for Karen A. Lillycrop: ORCID iD
ORCID for Graham C. Burdge: ORCID iD
ORCID for Emma Garratt: ORCID iD
ORCID for Hazel M. Inskip: ORCID iD
ORCID for Cyrus Cooper: ORCID iD

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Date deposited: 19 Apr 2012 13:35
Last modified: 27 Aug 2017 00:45

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Author: Alan Sheppard
Author: Peter D. Gluckman
Author: Cameron McClean
Author: Joanne Rodford
Author: Joanne L. Slater-Jefferies
Author: Emma Garratt ORCID iD
Author: Sarah R. Crozier
Author: B. Starling Emerald
Author: Hazel M. Inskip ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Mark A. Hanson

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