Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium

Leanne K. Küpers, Sílvia Fernández-Barrés, Aayah Nounu, Chloe Friedman, Ruby Fore, Giulia Mancano, Dana Dabelea, Sheryl L. Rifas-Shiman, Rosa H. Mulder, Emily Oken, Laura Johnson, Mariona Bustamante, Vincent W.V. Jaddoe, Marie France Hivert, Anne P. Starling, Jeanne H.M. de Vries, Gemma C. Sharp, Martine Vrijheid, Janine F. Felix*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Scopus)
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Higher adherence to the Mediterranean diet during pregnancy is related to a lower risk of preterm birth and to better offspring cardiometabolic health. DNA methylation may be an underlying biological mechanism. We evaluated whether maternal adherence to the Mediterranean diet was associated with offspring cord blood DNA methylation. We meta-analysed epigenome-wide association studies (EWAS) of maternal adherence to the Mediterranean diet during pregnancy and offspring cord blood DNA methylation in 2802 mother–child pairs from five cohorts. We calculated the relative Mediterranean diet (rMED) score with range 0–18 and an adjusted rMED excluding alcohol (rMEDp, range 0–16). DNA methylation was measured using Illumina 450K arrays. We used robust linear regression modelling adjusted for child sex, maternal education, age, smoking, body mass index, energy intake, batch, and cell types. We performed several functional analyses and examined the persistence of differential DNA methylation into childhood (4.5–7.8 y). rMEDp was associated with cord blood DNA methylation at cg23757341 (0.064% increase in DNA methylation per 1-point increase in the rMEDp score, SE = 0.011, P = 2.41 × 10−8). This cytosine–phosphate–guanine (CpG) site maps to WNT5B, associated with adipogenesis and glycaemic phenotypes. We did not identify associations with childhood gene expression, nor did we find enriched biological pathways. The association did not persist into childhood. In this meta-analysis, maternal adherence to the Mediterranean diet (excluding alcohol) during pregnancy was associated with cord blood DNA methylation level at cg23757341. Potential mediation of DNA methylation in associations with offspring health requires further study.

Original languageEnglish
Pages (from-to)1419-1431
Number of pages13
Issue number11
Publication statusPublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by the Foundation for the National Institutes of Health [R01 HD034568, UH3 OD023286, R01 NR013945, R01 HL111108]; Joint Programming Initiative A healthy diet for a healthy life [529051023, MR/S036520/1, 529051022, MR/S036520/1, MR/S036520/1]; National Institute of Environmental Health Sciences [R00ES025817]; National institute of diabetes and digestive and kidney diseases [R01DK076648]; National Institutes of Health Office of the Director [UH3OD023248]; Horizon 2020 research and innovation [874739, 733206, 848158, 824989]; Medical Research Council [MR/S009310/1]. Cohort-specific acknowledgements are stated in the Supplementary File, all authors declare no conflicts of interest. LKK and JFF designed the research; LKK, SFB, AN, APS, CF, RF conducted cohort-specific EWAS; LKK meta-analysed the summary statistics from all cohort-specific EWAS, which was independently shadowed by SFB. LKK and JFF wrote the paper; LKK has primary responsibility for the final content. All authors critically reviewed and approved the final manuscript.

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.


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