Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Darina Czamara; Abdel Abdellaoui; Aartjan T.F. Beekman; Eske M. Derks; Conor V. Dolan; Jouke Jan Hottenga; Rick Jansen; Hamdi Mbarek; Christel M. Middeldorp; Yuri Milaneschi; Michel G. Nivard; Danielle Posthuma; Dorret I. Boomsma; Brenda W.J.H. Penninx; Elisabeth B. Binder; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41467-019-10461-0

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Darina Czamara, Abdel Abdellaoui, Aartjan T.F. Beekman, Eske M. Derks, Conor V. Dolan, Jouke Jan Hottenga, Rick Jansen, Hamdi Mbarek, Christel M. Middeldorp, Yuri Milaneschi, Michel G. Nivard, Danielle Posthuma, Dorret I. Boomsma, Brenda W.J.H. Penninx, Elisabeth B. Binder^*, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Original language	English
Article number	2548
Pages (from-to)	1-18
Number of pages	18
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10461-0
Publication status	Published - 11 Jun 2019

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10.1038/s41467-019-10461-0

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Czamara, D., Abdellaoui, A., Beekman, A. T. F., Derks, E. M., Dolan, C. V., Hottenga, J. J., Jansen, R., Mbarek, H., Middeldorp, C. M., Milaneschi, Y., Nivard, M. G., Posthuma, D., Boomsma, D. I., Penninx, B. W. J. H., Binder, E. B., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2019). Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications, 10(1), 1-18. [2548]. https://doi.org/10.1038/s41467-019-10461-0

Czamara, Darina ; Abdellaoui, Abdel ; Beekman, Aartjan T.F. ; Derks, Eske M. ; Dolan, Conor V. ; Hottenga, Jouke Jan ; Jansen, Rick ; Mbarek, Hamdi ; Middeldorp, Christel M. ; Milaneschi, Yuri ; Nivard, Michel G. ; Posthuma, Danielle ; Boomsma, Dorret I. ; Penninx, Brenda W.J.H. ; Binder, Elisabeth B. ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. / Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. In: Nature Communications. 2019 ; Vol. 10, No. 1. pp. 1-18.

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abstract = "Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.",

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year = "2019",

month = jun,

day = "11",

doi = "10.1038/s41467-019-10461-0",

language = "English",

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journal = "Nature Communications",

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publisher = "Nature Publishing Group",

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Czamara, D, Abdellaoui, A, Beekman, ATF, Derks, EM, Dolan, CV , Hottenga, JJ , Jansen, R , Mbarek, H, Middeldorp, CM, Milaneschi, Y, Nivard, MG , Posthuma, D , Boomsma, DI, Penninx, BWJH, Binder, EB & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2019, 'Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns', Nature Communications, vol. 10, no. 1, 2548, pp. 1-18. https://doi.org/10.1038/s41467-019-10461-0

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. / Czamara, Darina; Abdellaoui, Abdel; Beekman, Aartjan T.F.; Derks, Eske M.; Dolan, Conor V.; Hottenga, Jouke Jan ; Jansen, Rick ; Mbarek, Hamdi; Middeldorp, Christel M.; Milaneschi, Yuri; Nivard, Michel G.; Posthuma, Danielle ; Boomsma, Dorret I.; Penninx, Brenda W.J.H.; Binder, Elisabeth B.; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Nature Communications, Vol. 10, No. 1, 2548, 11.06.2019, p. 1-18.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

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AU - Crawford, Gregory E.

AU - Davies, Gail

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AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

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AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

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AU - Xi, Hualin S.

AU - Yang, Jian

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AU - Dannlowski, Udo

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AU - Heath, Andrew C.

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AU - Tiemeier, Henning

AU - Uher, Rudolf

AU - Völzke, Henry

AU - Weissman, Myrna M.

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AU - Levinson, Douglas F.

AU - Breen, Gerome

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AU - Sullivan, Patrick F.

AU - Räikkönen, Katri

AU - Binder, Elisabeth B.

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

PY - 2019/6/11

Y1 - 2019/6/11

N2 - Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

AB - Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

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UR - http://www.scopus.com/inward/citedby.url?scp=85067229888&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-10461-0

DO - 10.1038/s41467-019-10461-0

M3 - Article

C2 - 31186427

VL - 10

SP - 1

EP - 18

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 2548

ER -

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

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