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

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to JournalArticleAcademicpeer-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 languageEnglish
Article number2548
Pages (from-to)1-18
Number of pages18
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 11 Jun 2019

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methylation
DNA Methylation
Fetal Blood
blood
Blood
deoxyribonucleic acid
Genotype
Genetic Epigenesis
Methylation
Genome-Wide Association Study
Information use
disorders
interactions

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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. pp. 1-18.
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}

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, 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. / Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

In: Nature Communications, Vol. 10, 2548, 11.06.2019, p. 1-18.

Research output: Contribution to JournalArticleAcademicpeer-review

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.

AU - Bacanu, Silviu Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T.F.

AU - Bigdeli, Tim B.

AU - Blackwood, Douglas H.R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni Kim

AU - Coleman, Jonathan R.I.

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

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Goes, Fernando S.

AU - Gordon, Scott D.

AU - Grove, Jakob

AU - Hall, Lynsey S.

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

AU - Horn, Carsten

AU - Hottenga, Jouke Jan

AU - Hougaard, David M.

AU - Ising, Marcus

AU - Jansen, Rick

AU - Jorgenson, Eric

AU - Knowles, James A.

AU - Kohane, Isaac S.

AU - Kraft, Julia

AU - Kretzschmar, Warren W.

AU - Krogh, Jesper

AU - Kutalik, Zoltán

AU - Li, Yihan

AU - Lind, Penelope A.

AU - MacIntyre, Donald J.

AU - MacKinnon, Dean F.

AU - Maier, Robert M.

AU - Maier, Wolfgang

AU - Marchini, Jonathan

AU - Mbarek, Hamdi

AU - McGrath, Patrick

AU - McGuffin, Peter

AU - Medland, Sarah E.

AU - Mehta, Divya

AU - Middeldorp, Christel M.

AU - Mihailov, Evelin

AU - Milaneschi, Yuri

AU - Milani, Lili

AU - Mondimore, Francis M.

AU - Montgomery, Grant W.

AU - Mostafavi, Sara

AU - Mullins, Niamh

AU - Nauck, Matthias

AU - Ng, Bernard

AU - Nivard, Michel G.

AU - Nyholt, Dale R.

AU - O’Reilly, Paul F.

AU - Oskarsson, Hogni

AU - Owen, Michael J.

AU - Painter, Jodie N.

AU - Pedersen, Carsten Bøcker

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

AU - Steinberg, Stacy

AU - Streit, Fabian

AU - Strohmaier, Jana

AU - Tansey, Katherine E.

AU - Teismann, Henning

AU - Teumer, Alexander

AU - Thompson, Wesley

AU - Thomson, Pippa A.

AU - Thorgeirsson, Thorgeir E.

AU - Traylor, Matthew

AU - Treutlein, Jens

AU - Trubetskoy, Vassily

AU - Uitterlinden, André G.

AU - Umbricht, Daniel

AU - Van der Auwera, Sandra

AU - van Hemert, Albert M.

AU - Viktorin, Alexander

AU - Visscher, Peter M.

AU - Wang, Yunpeng

AU - Webb, Bradley T.

AU - Weinsheimer, Shantel Marie

AU - Wellmann, Jürgen

AU - Willemsen, Gonneke

AU - Witt, Stephanie H.

AU - Wu, Yang

AU - Xi, Hualin S.

AU - Yang, Jian

AU - Zhang, Futao

AU - Arolt, Volker

AU - Baune, Bernhard T.

AU - Berger, Klaus

AU - Boomsma, Dorret I.

AU - Cichon, Sven

AU - Dannlowski, Udo

AU - de Geus, E. J.C.

AU - DePaulo, J. Raymond

AU - Domenici, Enrico

AU - Domschke, Katharina

AU - Esko, Tõnu

AU - Grabe, Hans J.

AU - Hamilton, Steven P.

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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SP - 1

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JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

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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. Nature Communications. 2019 Jun 11;10:1-18. 2548. https://doi.org/10.1038/s41467-019-10461-0