The emerging landscape of dynamic DNA methylation in early childhood

Cheng-Jian Xu; Marc Jan Bonder; Cilla Soderhall; Mariona Bustamante; Nour Baiz; Ulrike Gehring; Soesma A. Jankipersadsing; Pieter van der Vlies; Cleo C. van Diemen; Bianca van Rijkom; Jocelyne Just; Inger Kull; Juha Kere; Josep Maria Anto; Jean Bousquet; Alexandra Zhernakova; Cisca Wijmenga; Isabella Annesi-Maesano; Jordi Sunyer; Erik Melen; Yang Li; Dirkje S. Postma; Gerard H. Koppelman

doi:10.1186/s12864-016-3452-1

The emerging landscape of dynamic DNA methylation in early childhood

Cheng-Jian Xu, Marc Jan Bonder, Cilla Soderhall, Mariona Bustamante, Nour Baiz, Ulrike Gehring, Soesma A. Jankipersadsing, Pieter van der Vlies, Cleo C. van Diemen, Bianca van Rijkom, Jocelyne Just, Inger Kull, Juha Kere, Josep Maria Anto, Jean Bousquet, Alexandra Zhernakova, Cisca Wijmenga, Isabella Annesi-Maesano, Jordi Sunyer, Erik MelenYang Li, Dirkje S. Postma, Gerard H. Koppelman

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Abstract

Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.

Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho <1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease.

Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.

Original language	English
Pages (from-to)	25
Number of pages	11
Journal	BMC Genomics
Volume	18
Issue number	25
DOIs	https://doi.org/10.1186/s12864-016-3452-1
Publication status	Published - 5-Jan-2017

Keywords

DNA methylation
Aging
Methylation quantitative trait loci
Maternal smoking
D-ASPARTATE
AGE
DISEASE
ASTHMA
COHORT
METAANALYSIS
POPULATION
MICROARRAY
NEWBORNS
PROJECT

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Additional file 5: of The emerging landscape of dynamic DNA methylation in early childhood
Annesi-Maesano, I. (Contributor), Kull, I. (Contributor), Just, J. (Contributor), Baïz, N. (Contributor), Sunyer, J. (Contributor), Jankipersadsing, S. A. (Contributor), van der Vlies, P. (Contributor), Bonder, M. J. (Contributor), Koppelman, G. H. (Contributor), Bustamante, M. (Contributor), Antó, J. M. (Contributor), Wijmenga, C. (Contributor), Xu, C.-J. (Contributor), Bousquet, J. (Contributor), van Diemen, C. (Contributor), Zhernakova, S. (Contributor), Gehring, U. (Contributor), Li, Y. (Contributor), Rijkom, B. (Contributor), Postma, D. (Contributor), Melén, E. (Contributor), Kere, J. (Contributor) & Söderhäll, C. (Contributor), University of Groningen, 6-Jan-2017
DOI: 10.6084/m9.figshare.c.3659303_d5.v1, https://doi.org/10.6084%2Fm9.figshare.c.3659303_d5.v1
Dataset
Additional file 3: of The emerging landscape of dynamic DNA methylation in early childhood
Xu, C.-J. (Contributor), Bonder, M. J. (Contributor), Söderhäll, C. (Contributor), Just, J. (Contributor), Postma, D. (Contributor), Koppelman, G. H. (Contributor), Bustamante, M. (Contributor), Gehring, U. (Contributor), van Diemen, C. (Contributor), Baïz, N. (Contributor), Melén, E. (Contributor), Zhernakova, S. (Contributor), Bousquet, J. (Contributor), Rijkom, B. (Contributor), Annesi-Maesano, I. (Contributor), Antó, J. M. (Contributor), Li, Y. (Contributor), Kull, I. (Contributor), Wijmenga, C. (Contributor), Kere, J. (Contributor), Jankipersadsing, S. A. (Contributor), van der Vlies, P. (Contributor) & Sunyer, J. (Contributor), University of Groningen, 5-Jan-2017
DOI: 10.6084/m9.figshare.c.3659303_d2.v1
Dataset
Additional file 5: of The emerging landscape of dynamic DNA methylation in early childhood
Xu, C.-J. (Creator), Bonder, M. J. (Creator), Söderhäll, C. (Creator), Bustamante, M. (Contributor), Baïz, N. (Creator), Gehring, U. (Creator), Jankipersadsing, S. A. (Contributor), van der Vlies, P. (Contributor), van Diemen, C. (Contributor), Rijkom, B. (Contributor), Just, J. (Creator), Kull, I. (Creator), Kere, J. (Creator), Antó, J. M. (Creator), Bousquet, J. (Creator), Zhernakova, S. (Creator), Wijmenga, C. (Creator), Annesi-Maesano, I. (Creator), Sunyer, J. (Creator), Melén, E. (Creator), Li, Y. (Creator), Postma, D. (Creator) & Koppelman, G. H. (Creator), figshare, 5-Jan-2017
DOI: 10.6084/m9.figshare.c.3659303_d5
Dataset

Cite this

Xu, C.-J., Bonder, M. J., Soderhall, C., Bustamante, M., Baiz, N., Gehring, U., Jankipersadsing, S. A., van der Vlies, P., van Diemen, C. C., van Rijkom, B., Just, J., Kull, I., Kere, J., Anto, J. M., Bousquet, J., Zhernakova, A., Wijmenga, C., Annesi-Maesano, I., Sunyer, J., ... Koppelman, G. H. (2017). The emerging landscape of dynamic DNA methylation in early childhood. BMC Genomics, 18(25), 25. https://doi.org/10.1186/s12864-016-3452-1

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title = "The emerging landscape of dynamic DNA methylation in early childhood",

abstract = "Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho <1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease.Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.",

keywords = "DNA methylation, Aging, Methylation quantitative trait loci, Maternal smoking, D-ASPARTATE, AGE, DISEASE, ASTHMA, COHORT, METAANALYSIS, POPULATION, MICROARRAY, NEWBORNS, PROJECT",

author = "Cheng-Jian Xu and Bonder, {Marc Jan} and Cilla Soderhall and Mariona Bustamante and Nour Baiz and Ulrike Gehring and Jankipersadsing, {Soesma A.} and {van der Vlies}, Pieter and {van Diemen}, {Cleo C.} and {van Rijkom}, Bianca and Jocelyne Just and Inger Kull and Juha Kere and Anto, {Josep Maria} and Jean Bousquet and Alexandra Zhernakova and Cisca Wijmenga and Isabella Annesi-Maesano and Jordi Sunyer and Erik Melen and Yang Li and Postma, {Dirkje S.} and Koppelman, {Gerard H.}",

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Xu, C-J, Bonder, MJ, Soderhall, C, Bustamante, M, Baiz, N, Gehring, U, Jankipersadsing, SA, van der Vlies, P, van Diemen, CC, van Rijkom, B, Just, J, Kull, I, Kere, J, Anto, JM, Bousquet, J, Zhernakova, A , Wijmenga, C, Annesi-Maesano, I, Sunyer, J, Melen, E, Li, Y, Postma, DS & Koppelman, GH 2017, 'The emerging landscape of dynamic DNA methylation in early childhood', BMC Genomics, vol. 18, no. 25, pp. 25. https://doi.org/10.1186/s12864-016-3452-1

TY - JOUR

T1 - The emerging landscape of dynamic DNA methylation in early childhood

AU - Xu, Cheng-Jian

AU - Bonder, Marc Jan

AU - Soderhall, Cilla

AU - Bustamante, Mariona

AU - Baiz, Nour

AU - Gehring, Ulrike

AU - Jankipersadsing, Soesma A.

AU - van der Vlies, Pieter

AU - van Diemen, Cleo C.

AU - van Rijkom, Bianca

AU - Just, Jocelyne

AU - Kull, Inger

AU - Kere, Juha

AU - Anto, Josep Maria

AU - Bousquet, Jean

AU - Zhernakova, Alexandra

AU - Wijmenga, Cisca

AU - Annesi-Maesano, Isabella

AU - Sunyer, Jordi

AU - Melen, Erik

AU - Li, Yang

AU - Postma, Dirkje S.

AU - Koppelman, Gerard H.

PY - 2017/1/5

Y1 - 2017/1/5

N2 - Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho <1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease.Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.

AB - Background: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood.Results: By analysing 538 paired DNA blood samples from children at birth and at 4-5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of rho <1.14x10(-7). Genes with an increase in age-differential methylation were enriched in pathways related to 'development', and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease.Conclusion: Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.

KW - DNA methylation

KW - Aging

KW - Methylation quantitative trait loci

KW - Maternal smoking

KW - D-ASPARTATE

KW - AGE

KW - DISEASE

KW - ASTHMA

KW - COHORT

KW - METAANALYSIS

KW - POPULATION

KW - MICROARRAY

KW - NEWBORNS

KW - PROJECT

U2 - 10.1186/s12864-016-3452-1

DO - 10.1186/s12864-016-3452-1

M3 - Article

C2 - 28056824

SN - 1471-2164

VL - 18

SP - 25

JO - BMC Genomics

JF - BMC Genomics

IS - 25

ER -

The emerging landscape of dynamic DNA methylation in early childhood

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Keywords

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Additional file 5: of The emerging landscape of dynamic DNA methylation in early childhood

Additional file 3: of The emerging landscape of dynamic DNA methylation in early childhood

Additional file 5: of The emerging landscape of dynamic DNA methylation in early childhood

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