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DNA methylation trajectories during pregnancy

DNA methylation trajectories during pregnancy
DNA methylation trajectories during pregnancy

There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P <.05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P <.05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.

Cohort, DNA methylation, Illumina EPIC and Infinium chip, pregnancy
Gruzieva, Olena
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Merid, Simon Kebede
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Chen, Su
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Mukherjee, Nandini
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Hedman, Anna M.
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Almqvist, Catarina
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Andolf, Ellika
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Jiang, Yu
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Kere, Juha
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Scheynius, Annika
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Söderhäll, Cilla
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Ullemar, Vilhelmina
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Karmaus, Wilfried
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Melén, Erik
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Arshad, Syed Hasan
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Pershagen, Göran
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Gruzieva, Olena
0865d16b-2fdc-4e58-b834-a9fd22283ca5
Merid, Simon Kebede
97470f65-a3fd-4aaf-8637-e0dea6f1114e
Chen, Su
ffb45732-4c5d-4329-afa3-9cab1c38fd1c
Mukherjee, Nandini
f64f02d6-2fd0-40db-88ee-5f85b59b8e0b
Hedman, Anna M.
1a78c62e-8caf-4b18-b275-3a991a5e41f6
Almqvist, Catarina
68bd5bec-1e94-4252-96b8-485c8308561c
Andolf, Ellika
218974e3-872a-4ee9-9ff0-4721d1dc09a8
Jiang, Yu
4fa0a27b-8c06-4988-832a-8f5fb3a3f1ec
Kere, Juha
57c301de-f111-4552-a585-13eed945bdfc
Scheynius, Annika
76a441c8-85ae-4c21-adc1-fd84f2b6eb43
Söderhäll, Cilla
5117b3f6-4192-4cd7-b81f-427bead07bd0
Ullemar, Vilhelmina
c98d98d3-3348-4ccf-aff2-343ae9988222
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Melén, Erik
c7ee5423-aed5-4905-80b3-65bc07192e0c
Arshad, Syed Hasan
917e246d-2e60-472f-8d30-94b01ef28958
Pershagen, Göran
5680dad3-cd15-4752-a61a-49f3502953ef

Gruzieva, Olena, Merid, Simon Kebede, Chen, Su, Mukherjee, Nandini, Hedman, Anna M., Almqvist, Catarina, Andolf, Ellika, Jiang, Yu, Kere, Juha, Scheynius, Annika, Söderhäll, Cilla, Ullemar, Vilhelmina, Karmaus, Wilfried, Melén, Erik, Arshad, Syed Hasan and Pershagen, Göran (2019) DNA methylation trajectories during pregnancy. Epigenetics Insights, 12. (doi:10.1177/2516865719867090).

Record type: Article

Abstract

There is emerging evidence on DNA methylation (DNAm) variability over time; however, little is known about dynamics of DNAm patterns during pregnancy. We performed an epigenome-wide longitudinal DNAm study of a well-characterized sample of young women from the Swedish Born into Life study, with repeated blood sampling before, during and after pregnancy (n = 21), using the Illumina Infinium MethylationEPIC array. We conducted a replication in the Isle of Wight third-generation birth cohort (n = 27), using the Infinium HumanMethylation450k BeadChip. We identified 196 CpG sites displaying intra-individual longitudinal change in DNAm with a false discovery rate (FDR) P <.05. Most of these (91%) showed a decrease in average methylation levels over the studied period. We observed several genes represented by ⩾3 differentially methylated CpGs: HOXB3, AVP, LOC100996291, and MicroRNA 10a. Of 36 CpGs available in the replication cohort, 17 were replicated, all but 2 with the same direction of association (replication P <.05). Biological pathway analysis demonstrated that FDR-significant CpGs belong to genes overrepresented in metabolism-related pathways, such as adipose tissue development, regulation of insulin receptor signaling, and mammary gland fat development. These results contribute to a better understanding of the biological mechanisms underlying important physiological alterations and adaptations for pregnancy and lactation.

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Accepted/In Press date: 10 July 2019
Published date: 13 August 2019
Keywords: Cohort, DNA methylation, Illumina EPIC and Infinium chip, pregnancy

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Local EPrints ID: 434019
URI: http://eprints.soton.ac.uk/id/eprint/434019
PURE UUID: e42a67eb-8bdf-4d93-9e46-e3a6de14800c

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Date deposited: 11 Sep 2019 16:30
Last modified: 07 Oct 2020 01:01

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Contributors

Author: Olena Gruzieva
Author: Simon Kebede Merid
Author: Su Chen
Author: Nandini Mukherjee
Author: Anna M. Hedman
Author: Catarina Almqvist
Author: Ellika Andolf
Author: Yu Jiang
Author: Juha Kere
Author: Annika Scheynius
Author: Cilla Söderhäll
Author: Vilhelmina Ullemar
Author: Wilfried Karmaus
Author: Erik Melén
Author: Göran Pershagen

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