Maternal gestational weight gain and DNA methylation in young women: Application of life course mediation methods

Jonathan Y. Huang; David S. Siscovick; Hagit Hochner; Yechiel Friedlander; Daniel A. Enquobahrie

doi:10.2217/epi-2017-0085

Maternal gestational weight gain and DNA methylation in young women: Application of life course mediation methods

Jonathan Y. Huang, David S. Siscovick, Hagit Hochner, Yechiel Friedlander, Daniel A. Enquobahrie

Research output: Contribution to journal › Article › peer-review

Abstract

Aim: To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Methods: Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Results: Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β =-1.1% per quartile; 95% CI:-2.0,-0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. Conclusion: We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.

Original language	English
Pages (from-to)	1559-1571
Number of pages	13
Journal	Epigenomics
Volume	9
Issue number	12
DOIs	https://doi.org/10.2217/epi-2017-0085
State	Published - Dec 2017
Externally published	Yes

Keywords

ABCA1
DNA methylation
DOHaD
candidate gene
gestational weight gain
intermediate confounding
marginal structural model
parametric g-formula

All Science Journal Classification (ASJC) codes

Genetics
Cancer Research

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10.2217/epi-2017-0085

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title = "Maternal gestational weight gain and DNA methylation in young women: Application of life course mediation methods",

abstract = "Aim: To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Methods: Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Results: Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β =-1.1% per quartile; 95% CI:-2.0,-0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. Conclusion: We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.",

keywords = "ABCA1, DNA methylation, DOHaD, candidate gene, gestational weight gain, intermediate confounding, marginal structural model, parametric g-formula",

author = "Huang, {Jonathan Y.} and Siscovick, {David S.} and Hagit Hochner and Yechiel Friedlander and Enquobahrie, {Daniel A.}",

note = "Publisher Copyright: {\textcopyright} 2017 Future Medicine Ltd.",

year = "2017",

month = dec,

doi = "10.2217/epi-2017-0085",

language = "الإنجليزيّة",

volume = "9",

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journal = "Epigenomics",

issn = "1750-1911",

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number = "12",

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T1 - Maternal gestational weight gain and DNA methylation in young women

T2 - Application of life course mediation methods

AU - Huang, Jonathan Y.

AU - Siscovick, David S.

AU - Hochner, Hagit

AU - Friedlander, Yechiel

AU - Enquobahrie, Daniel A.

PY - 2017/12

Y1 - 2017/12

N2 - Aim: To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Methods: Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Results: Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β =-1.1% per quartile; 95% CI:-2.0,-0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. Conclusion: We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.

AB - Aim: To investigate the role of maternal gestational weight gain (GWG) and prepregnancy BMI on programming offspring DNA methylation. Methods: Among 589 adult (age = 32) women participants of the Jerusalem Perinatal Study, we quantified DNA methylation in five candidate genes. We used inverse probability-weighting and parametric g-formula to estimate direct effects of maternal prepregnancy BMI and GWG on methylation. Results: Higher maternal GWG, but not prepregnancy BMI, was inversely related to offspring ABCA1 methylation (β =-1.1% per quartile; 95% CI:-2.0,-0.3) after accounting for ancestry, parental and offspring exposures. Total and controlled direct effects were nearly identical suggesting included offspring exposures did not mediate this relationship. Results were robust to sensitivity analyses for missing data and model specification. Conclusion: We find some support for epigenetic programming and highlight strengths and limitations of these methods relative to other prevailing approaches.

KW - ABCA1

KW - DNA methylation

KW - DOHaD

KW - candidate gene

KW - gestational weight gain

KW - intermediate confounding

KW - marginal structural model

KW - parametric g-formula

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U2 - 10.2217/epi-2017-0085

DO - 10.2217/epi-2017-0085

M3 - مقالة

C2 - 29106309

SN - 1750-1911

VL - 9

SP - 1559

EP - 1571

JO - Epigenomics

JF - Epigenomics

IS - 12

ER -

Maternal gestational weight gain and DNA methylation in young women: Application of life course mediation methods

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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