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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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

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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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J.C.} and DePaulo, {J. Raymond} and Enrico Domenici and Katharina Domschke and T{\~o}nu Esko and Grabe, {Hans J.} and Hamilton, {Steven P.} and Caroline Hayward and Heath, {Andrew C.} and Kendler, {Kenneth S.} and Stefan Kloiber and Glyn Lewis and Li, {Qingqin S.} and Susanne Lucae and Madden, {Pamela A.F.} and Magnusson, {Patrik K.} and Martin, {Nicholas G.} and McIntosh, {Andrew M.} and Andres Metspalu and Ole Mors and Mortensen, {Preben Bo} and Bertram M{\"u}ller-Myhsok and Merete Nordentoft and N{\"o}then, {Markus M.} and O{\textquoteright}Donovan, {Michael C.} and Paciga, {Sara A.} and Pedersen, {Nancy L.} and Penninx, {Brenda W.J.H.} and Perlis, {Roy H.} and Porteous, {David J.} and Potash, {James B.} and Martin Preisig and Marcella Rietschel and Catherine Schaefer and Schulze, {Thomas G.} and Smoller, {Jordan W.} and Kari Stefansson and Henning Tiemeier and Rudolf Uher and Henry V{\"o}lzke and Weissman, {Myrna M.} and Thomas Werge and Lewis, {Cathryn M.} and Levinson, {Douglas F.} and Gerome Breen and B{\o}rglum, {Anders D.} and Sullivan, {Patrick F.} and Katri R{\"a}ikk{\"o}nen and Binder, {Elisabeth B.} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium}",

year = "2019",

month = jun,

day = "11",

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

language = "English",

volume = "10",

pages = "1--18",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

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

TY - JOUR

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

AU - Czamara, Darina

AU - Eraslan, Gökçen

AU - Page, Christian M.

AU - Lahti, Jari

AU - Lahti-Pulkkinen, Marius

AU - Hämäläinen, Esa

AU - Kajantie, Eero

AU - Laivuori, Hannele

AU - Villa, Pia M.

AU - Reynolds, Rebecca M.

AU - Nystad, Wenche

AU - Håberg, Siri E.

AU - London, Stephanie J.

AU - O’Donnell, Kieran J.

AU - Garg, Elika

AU - Meaney, Michael J.

AU - Entringer, Sonja

AU - Wadhwa, Pathik D.

AU - Buss, Claudia

AU - Jones, Meaghan J.

AU - Lin, David T.S.

AU - MacIsaac, Julie L.

AU - Kobor, Michael S.

AU - Koen, Nastassja

AU - Zar, Heather J.

AU - Koenen, Karestan C.

AU - Dalvie, Shareefa

AU - Stein, Dan J.

AU - Kondofersky, Ivan

AU - Müller, Nikola S.

AU - Theis, Fabian J.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F.M.

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AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

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AU - Castelao, Enrique

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AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

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AU - Gaspar, Héléna A.

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AU - Hansen, Thomas F.

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AU - Homuth, Georg

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AU - Ising, Marcus

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AU - Jorgenson, Eric

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AU - Kohane, Isaac S.

AU - Kraft, Julia

AU - Kretzschmar, Warren W.

AU - Krogh, Jesper

AU - Kutalik, Zoltán

AU - Li, Yihan

AU - Lind, Penelope A.

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AU - MacKinnon, Dean F.

AU - Maier, Robert M.

AU - Maier, Wolfgang

AU - Marchini, Jonathan

AU - Mbarek, Hamdi

AU - McGrath, Patrick

AU - McGuffin, Peter

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AU - Pedersen, Marianne Giørtz

AU - Peterson, Roseann E.

AU - Pettersson, Erik

AU - Peyrot, Wouter J.

AU - Pistis, Giorgio

AU - Posthuma, Danielle

AU - Quiroz, Jorge A.

AU - Qvist, Per

AU - Rice, John P.

AU - Riley, Brien P.

AU - Rivera, Margarita

AU - Mirza, Saira Saeed

AU - Schoevers, Robert

AU - Schulte, Eva C.

AU - Shen, Ling

AU - Shi, Jianxin

AU - Shyn, Stanley I.

AU - Sigurdsson, Engilbert

AU - Sinnamon, Grant C.B.

AU - Smit, Johannes H.

AU - Smith, Daniel J.

AU - Stefansson, Hreinn

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AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Tansey, Katherine E.

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AU - Thorgeirsson, Thorgeir E.

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AU - Treutlein, Jens

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AU - van Hemert, Albert M.

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AU - Domenici, Enrico

AU - Domschke, Katharina

AU - Esko, Tõnu

AU - Grabe, Hans J.

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AU - Hayward, Caroline

AU - Heath, Andrew C.

AU - Kendler, Kenneth S.

AU - Kloiber, Stefan

AU - Lewis, Glyn

AU - Li, Qingqin S.

AU - Lucae, Susanne

AU - Madden, Pamela A.F.

AU - Magnusson, Patrik K.

AU - Martin, Nicholas G.

AU - McIntosh, Andrew M.

AU - Metspalu, Andres

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Müller-Myhsok, Bertram

AU - Nordentoft, Merete

AU - Nöthen, Markus M.

AU - O’Donovan, Michael C.

AU - Paciga, Sara A.

AU - Pedersen, Nancy L.

AU - Penninx, Brenda W.J.H.

AU - Perlis, Roy H.

AU - Porteous, David J.

AU - Potash, James B.

AU - Preisig, Martin

AU - Rietschel, Marcella

AU - Schaefer, Catherine

AU - Schulze, Thomas G.

AU - Smoller, Jordan W.

AU - Stefansson, Kari

AU - Tiemeier, Henning

AU - Uher, Rudolf

AU - Völzke, Henry

AU - Weissman, Myrna M.

AU - Werge, Thomas

AU - Lewis, Cathryn M.

AU - Levinson, Douglas F.

AU - Breen, Gerome

AU - Børglum, Anders D.

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

SN - 2041-1723

VL - 10

SP - 1

EP - 18

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2548

ER -

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

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