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
- PMID: 25855720
- PMCID: PMC4588865
- DOI: 10.1093/ije/dyv042
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
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.
Keywords: ALSPAC; ARIES; Epigenetic; causality; epigenome-wide association study; longitudinal; overnutrition; overweight; undernutrition.
© The Author 2015. Published by Oxford University Press on behalf of the International Epidemiological Association.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4588865/bin/dyv042f1p.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4588865/bin/dyv042f2p.gif)
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4588865/bin/dyv042f3p.gif)
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4588865/bin/dyv042f4p.gif)
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4588865/bin/dyv042f5p.gif)
Similar articles
-
The mediating effect of DNA methylation in the association between maternal sleep during pregnancy and offspring adiposity status: a prospective cohort study.Clin Epigenetics. 2022 May 20;14(1):66. doi: 10.1186/s13148-022-01284-w. Clin Epigenetics. 2022. PMID: 35596190 Free PMC article.
-
Childhood DNA methylation as a marker of early life rapid weight gain and subsequent overweight.Clin Epigenetics. 2021 Jan 12;13(1):8. doi: 10.1186/s13148-020-00952-z. Clin Epigenetics. 2021. PMID: 33436068 Free PMC article.
-
Exploring the causal effect of maternal pregnancy adiposity on offspring adiposity: Mendelian randomisation using polygenic risk scores.BMC Med. 2022 Feb 1;20(1):34. doi: 10.1186/s12916-021-02216-w. BMC Med. 2022. PMID: 35101027 Free PMC article.
-
Offspring body size and metabolic profile - effects of lifestyle intervention in obese pregnant women.Dan Med J. 2014 Jul;61(7):B4893. Dan Med J. 2014. PMID: 25123127 Review.
-
Maternal and paternal body mass index and offspring obesity: a systematic review.Ann Nutr Metab. 2013;63(1-2):32-41. doi: 10.1159/000350313. Epub 2013 Jul 23. Ann Nutr Metab. 2013. PMID: 23887153 Review.
Cited by
-
Integrative network analysis of differentially methylated regions to study the impact of gestational weight gain on maternal metabolism and fetal-neonatal growth.Genet Mol Biol. 2024 Mar 25;47(1):e20230203. doi: 10.1590/1678-4685-GMB-2023-0203. eCollection 2024. Genet Mol Biol. 2024. PMID: 38530405 Free PMC article.
-
Alterations of DNA methylation profile in peripheral blood of children with simple obesity.Health Inf Sci Syst. 2024 Mar 18;12(1):26. doi: 10.1007/s13755-024-00275-w. eCollection 2024 Dec. Health Inf Sci Syst. 2024. PMID: 38505098 Free PMC article.
-
Close Adherence to a Mediterranean Diet during Pregnancy Decreases Childhood Overweight/Obesity: A Prospective Study.Nutrients. 2024 Feb 14;16(4):532. doi: 10.3390/nu16040532. Nutrients. 2024. PMID: 38398856 Free PMC article.
-
DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes.Biomedicines. 2024 Jan 27;12(2):301. doi: 10.3390/biomedicines12020301. Biomedicines. 2024. PMID: 38397903 Free PMC article.
-
The Effect of Maternal Diet and Physical Activity on the Epigenome of the Offspring.Genes (Basel). 2024 Jan 6;15(1):76. doi: 10.3390/genes15010076. Genes (Basel). 2024. PMID: 38254965 Free PMC article. Review.
References
-
- Lawlor DA, Relton C, Sattar N, Nelson SM. Maternal adiposity - a determinant of perinatal and offspring outcomes? Nat Rev Endocrinol 2012;8:679–88. - PubMed
-
- Lawlor DA. The Society for Social Medicine John Pemberton Lecture 2011. Developmental overnutrition—an old hypothesis with new importance? Int J Epidemiol 2013;42:7–29. - PubMed
Publication types
MeSH terms
Grants and funding
- MR/M009351/1/MRC_/Medical Research Council/United Kingdom
- BB/I025263/1/Biotechnology and Biological Sciences Research Council/United Kingdom
- MC_UU_12013/2/MRC_/Medical Research Council/United Kingdom
- G0701594/MRC_/Medical Research Council/United Kingdom
- MC_UU_12013/1/MRC_/Medical Research Council/United Kingdom
- MC_PC_15018/MRC_/Medical Research Council/United Kingdom
- MC_UU_12013/5/MRC_/Medical Research Council/United Kingdom
- R01 DK103246/DK/NIDDK NIH HHS/United States
- MC_UU_12013_5/Medical Research Council/United Kingdom
- 02215/2/13/2/Wellcome Trust/United Kingdom
- 0701594/1/Medical Research Council/United Kingdom
- WT094529MA/Wellcome Trust/United Kingdom
- 102215/Wellcome Trust/United Kingdom
- MC_UU_12013_2/Medical Research Council/United Kingdom
- R01 DK10324/DK/NIDDK NIH HHS/United States
- BB/I025751/1/Biotechnology and Biological Sciences Research Council/United Kingdom
- WT083431MF/Wellcome Trust/United Kingdom
- MC_UU_12013/8/MRC_/Medical Research Council/United Kingdom
- MC_UU_12013_8/Medical Research Council/United Kingdom
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical