Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

Line Hjort; David Martino; Louise Groth Grunnet; Haroon Naeem; Jovana Maksimovic; Anders Henrik Olsson; Cuilin Zhang; Charlotte Ling; Sjurdur Frodi Olsen; Richard Saffery; Allan Arthur Vaag

doi:10.1172/jci.insight.122572

Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

Line Hjort, David Martino, Louise Groth Grunnet, Haroon Naeem, Jovana Maksimovic, Anders Henrik Olsson, Cuilin Zhang, Charlotte Ling, Sjurdur Frodi Olsen, Richard Saffery, Allan Arthur Vaag

37 Citations (Scopus)

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Abstract

Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.

Original language	English
Article number	e122572
Journal	JCI Insight
Volume	3
Issue number	17
Number of pages	15
DOIs	https://doi.org/10.1172/jci.insight.122572
Publication status	Published - 6 Sept 2018

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@article{531a37eb926d4c94bdebdb8ee2c84382,

title = "Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children",

abstract = "Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.",

author = "Line Hjort and David Martino and Grunnet, {Louise Groth} and Haroon Naeem and Jovana Maksimovic and Olsson, {Anders Henrik} and Cuilin Zhang and Charlotte Ling and Olsen, {Sjurdur Frodi} and Richard Saffery and Vaag, {Allan Arthur}",

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doi = "10.1172/jci.insight.122572",

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T1 - Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

AU - Hjort, Line

AU - Martino, David

AU - Grunnet, Louise Groth

AU - Naeem, Haroon

AU - Maksimovic, Jovana

AU - Olsson, Anders Henrik

AU - Zhang, Cuilin

AU - Ling, Charlotte

AU - Olsen, Sjurdur Frodi

AU - Saffery, Richard

AU - Vaag, Allan Arthur

PY - 2018/9/6

Y1 - 2018/9/6

N2 - Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.

AB - Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.

U2 - 10.1172/jci.insight.122572

DO - 10.1172/jci.insight.122572

M3 - Journal article

C2 - 30185669

SN - 2379-3708

VL - 3

JO - JCI Insight

JF - JCI Insight

IS - 17

M1 - e122572

ER -

Gestational diabetes and maternal obesity are associated with epigenome-wide methylation changes in children

Abstract

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