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

doi:10.1080/15592294.2022.2038412

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

Pediatrics

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Abstract

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 language	English
Pages (from-to)	1419-1431
Number of pages	13
Journal	Epigenetics
Volume	17
Issue number	11
DOIs	https://doi.org/10.1080/15592294.2022.2038412
Publication status	Published - 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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Maternal Mediterranean diet in pregnancy and newborn DNA methylation a meta analysis in the PACE ConsortiumFinal published version, 1.02 MBLicence: CC BY

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Küpers, L. K., Fernández-Barrés, S., Nounu, A., Friedman, C., Fore, R., Mancano, G., Dabelea, D., Rifas-Shiman, S. L., Mulder, R. H., Oken, E., Johnson, L., Bustamante, M., Jaddoe, V. W. V., Hivert, M. F., Starling, A. P., de Vries, J. H. M., Sharp, G. C., Vrijheid, M., & Felix, J. F. (2022). Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium. Epigenetics, 17(11), 1419-1431. https://doi.org/10.1080/15592294.2022.2038412

@article{47fa53daae2542b988dd3e72b8d7a9d7,

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

abstract = "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.",

author = "K{\"u}pers, {Leanne K.} and S{\'i}lvia Fern{\'a}ndez-Barr{\'e}s and Aayah Nounu and Chloe Friedman and Ruby Fore and Giulia Mancano and Dana Dabelea and Rifas-Shiman, {Sheryl L.} and Mulder, {Rosa H.} and Emily Oken and Laura Johnson and Mariona Bustamante and Jaddoe, {Vincent W.V.} and Hivert, {Marie France} and Starling, {Anne P.} and {de Vries}, {Jeanne H.M.} and Sharp, {Gemma C.} and Martine Vrijheid and Felix, {Janine F.}",

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: {\textcopyright} 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2022",

month = nov,

doi = "10.1080/15592294.2022.2038412",

language = "English",

volume = "17",

pages = "1419--1431",

journal = "Epigenetics",

issn = "1559-2294",

publisher = "Taylor & Francis Ltd",

number = "11",

}

Küpers, LK, Fernández-Barrés, S, Nounu, A, Friedman, C, Fore, R, Mancano, G, Dabelea, D, Rifas-Shiman, SL, Mulder, RH, Oken, E, Johnson, L, Bustamante, M, Jaddoe, VWV, Hivert, MF, Starling, AP, de Vries, JHM, Sharp, GC, Vrijheid, M & Felix, JF 2022, 'Maternal Mediterranean diet in pregnancy and newborn DNA methylation: a meta-analysis in the PACE Consortium', Epigenetics, vol. 17, no. 11, pp. 1419-1431. https://doi.org/10.1080/15592294.2022.2038412

TY - JOUR

T1 - Maternal Mediterranean diet in pregnancy and newborn DNA methylation

T2 - a meta-analysis in the PACE Consortium

AU - Küpers, Leanne K.

AU - Fernández-Barrés, Sílvia

AU - Nounu, Aayah

AU - Friedman, Chloe

AU - Fore, Ruby

AU - Mancano, Giulia

AU - Dabelea, Dana

AU - Rifas-Shiman, Sheryl L.

AU - Mulder, Rosa H.

AU - Oken, Emily

AU - Johnson, Laura

AU - Bustamante, Mariona

AU - Jaddoe, Vincent W.V.

AU - Hivert, Marie France

AU - Starling, Anne P.

AU - de Vries, Jeanne H.M.

AU - Sharp, Gemma C.

AU - Vrijheid, Martine

AU - Felix, Janine F.

N1 - 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.

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

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SN - 1559-2294

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JO - Epigenetics

JF - Epigenetics

IS - 11

ER -

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

Abstract

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