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

Supplementary data

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Financial & competing interests disclosure

This work was supported by an Integrated Health Seed Grant 2013–2014 from the University of Washington Global Women, Adolescents, and Children (WACh) program and grants T32HD052462, K01HL103174 and R01HL088884 from the National Institutes of Health. This work was also supported by Operating Grant #115214 and an Institute of Nutrition, Metabolism, and Diabetes Travel Award from the Canadian Institutes of Health Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by an Integrated Health Seed Grant 2013–2014 from the University of Washington Global Women, Adolescents, and Children (WACh) program and grants T32HD052462, K01HL103174 and R01HL088884 from the National Institutes of Health. This work was also supported by Operating Grant #115214 and an Institute of Nutrition, Metabolism, and Diabetes Travel Award from the Canadian Institutes of Health Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.