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Journal Articles Nature Communications Year : 2019

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

Darina Czamara (1) , Gökçen Eraslan (2) , Christian M Page (3) , Jari Lahti (4) , Marius Lahti-Pulkkinen (4) , Esa Hämäläinen (4) , Eero Kajantie , Hannele Laivuori , Pia M Villa , Rebecca M Reynolds , Wenche Nystad , Siri E Håberg , Stephanie J London , Kieran J O’donnell , Elika Garg , Michael J Meaney , Sonja Entringer , Pathik D Wadhwa , Claudia Buss , Meaghan J Jones , David T S Lin , Julie L Macisaac , Michael S Kobor , Nastassja Koen , Heather J Zar , Karestan C Koenen , Shareefa Dalvie , Dan J Stein , Ivan Kondofersky , Nikola S Müller , Fabian J Theis , Naomi R Wray , Stephan Ripke , Manuel Mattheisen , Maciej Trzaskowski , Enda M Byrne , Abdel Abdellaoui , Mark J Adams , Esben Agerbo , Tracy M Air , Till F M Andlauer , Silviu-Alin Bacanu , Marie Bækvad-Hansen , Aartjan T F Beekman , Tim B Bigdeli , Douglas H R Blackwood , Julien Bryois , Henriette N Buttenschøn , Jonas Bybjerg-Grauholm , Na Cai , Enrique Castelao , Jane Hvarregaard Christensen , Toni-Kim Clarke , Jonathan R I Coleman , Lucía Colodro-Conde , Baptiste Couvy-Duchesne (5) , Nick Craddock , Gregory E Crawford , Gail Davies , Ian J Deary , Franziska Degenhardt , Eske M Derks , Nese Direk , Conor V Dolan , Erin C Dunn , Thalia C Eley , Valentina Escott-Price , Farnush Farhadi Hassan Kiadeh , Hilary K Finucane , Andreas J Forstner , Josef Frank , Héléna A Gaspar , Michael Gill , Fernando S Goes , Scott D Gordon , Jakob Grove , Lynsey S Hall , Christine Søholm Hansen , Thomas F Hansen , Stefan Herms , Ian B Hickie , Per Hoffmann , Georg Homuth , Carsten Horn , Jouke-Jan Hottenga , David M Hougaard , Marcus Ising , Rick Jansen , Eric Jorgenson , James A Knowles , Isaac S Kohane , Julia Kraft , Warren W Kretzschmar , Jesper Krogh , Zoltán Kutalik , Yihan Li , Penelope A Lind , Donald J Macintyre , Dean F Mackinnon , Robert M Maier , Wolfgang Maier , Jonathan Marchini , Hamdi Mbarek , Patrick Mcgrath , Peter Mcguffin , Sarah E Medland , Divya Mehta , Christel M Middeldorp , Evelin Mihailov , Yuri Milaneschi , Lili Milani , Francis M Mondimore , Grant W Montgomery , Sara Mostafavi , Niamh Mullins , Matthias Nauck , Bernard Ng , Michel G Nivard , Dale R Nyholt , Paul F O’reilly , Hogni Oskarsson , Michael J Owen , Jodie N Painter , Carsten Bøcker Pedersen , Marianne Giørtz Pedersen , Roseann E Peterson , Erik Pettersson , Wouter J Peyrot , Giorgio Pistis , Danielle Posthuma , Jorge A Quiroz , Per Qvist , John P Rice , Brien P Riley , Margarita Rivera , Saira Saeed Mirza , Robert Schoevers , Eva C Schulte , Ling Shen , Jianxin Shi , Stanley I Shyn , Engilbert Sigurdsson , Grant C B Sinnamon , Johannes H Smit , Daniel J Smith , Hreinn Stefansson , Stacy Steinberg , Fabian Streit , Jana Strohmaier , Katherine E Tansey , Henning Teismann , Alexander Teumer , Wesley Thompson , Pippa A Thomson , Thorgeir E Thorgeirsson , Matthew Traylor , Jens Treutlein , Vassily Trubetskoy , André G Uitterlinden , Daniel Umbricht , Sandra van der Auwera , Albert M van Hemert , Alexander Viktorin , Peter M Visscher , Yunpeng Wang , Bradley T Webb , Shantel Marie Weinsheimer , Jürgen Wellmann , Gonneke Willemsen , Stephanie H Witt , Yang Wu , Hualin S Xi , Jian Yang , Futao Zhang , Volker Arolt , Bernhard T Baune , Klaus Berger , Dorret I Boomsma , Sven Cichon , Udo Dannlowski , E J C de Geus , J Raymond Depaulo , Enrico Domenici , Katharina Domschke , Tõnu Esko , Hans J Grabe , Steven P Hamilton , Caroline Hayward , Andrew C Heath , Kenneth S Kendler , Stefan Kloiber , Glyn Lewis , Qingqin S Li , Susanne Lucae , Pamela a F Madden , Patrik K Magnusson , Nicholas G Martin , Andrew M Mcintosh , Andres Metspalu , Ole Mors , Preben Bo Mortensen , Bertram Müller-Myhsok , Merete Nordentoft , Markus M Nöthen , Michael C O’donovan , Sara A Paciga , Nancy L Pedersen , Brenda W J H Penninx , Roy H Perlis , David J Porteous , James B Potash , Martin Preisig , Marcella Rietschel , Catherine Schaefer , Thomas G Schulze , Jordan W Smoller , Kari Stefansson , Henning Tiemeier , Rudolf Uher , Henry Völzke , Myrna M Weissman , Thomas Werge , Cathryn M Lewis , Douglas F Levinson , Gerome Breen , Anders D Børglum , Patrick F Sullivan , Katri Räikkönen , Elisabeth B Binder (1)
Darina Czamara
Christian M Page
Jari Lahti
Marius Lahti-Pulkkinen
Esa Hämäläinen
  • Function : Author
Eero Kajantie
  • Function : Author
Hannele Laivuori
Pia M Villa
  • Function : Author
Rebecca M Reynolds
  • Function : Author
Wenche Nystad
  • Function : Author
Siri E Håberg
  • Function : Author
Stephanie J London
Kieran J O’donnell
  • Function : Author
Elika Garg
Michael J Meaney
  • Function : Author
Sonja Entringer
  • Function : Author
Pathik D Wadhwa
  • Function : Author
Claudia Buss
Meaghan J Jones
  • Function : Author
David T S Lin
Julie L Macisaac
  • Function : Author
Michael S Kobor
  • Function : Author
Nastassja Koen
  • Function : Author
Heather J Zar
  • Function : Author
Karestan C Koenen
  • Function : Author
Shareefa Dalvie
  • Function : Author
Dan J Stein
  • Function : Author
Ivan Kondofersky
  • Function : Author
Nikola S Müller
  • Function : Author
Fabian J Theis
Naomi R Wray
  • Function : Author
Stephan Ripke
  • Function : Author
Manuel Mattheisen
  • Function : Author
Maciej Trzaskowski
  • Function : Author
Enda M Byrne
  • Function : Author
Abdel Abdellaoui
  • Function : Author
Mark J Adams
  • Function : Author
Esben Agerbo
  • Function : Author
Tracy M Air
  • Function : Author
Till F M Andlauer
  • Function : Author
Silviu-Alin Bacanu
  • Function : Author
Marie Bækvad-Hansen
  • Function : Author
Aartjan T F Beekman
  • Function : Author
Tim B Bigdeli
  • Function : Author
Douglas H R Blackwood
  • Function : Author
Julien Bryois
  • Function : Author
Henriette N Buttenschøn
  • Function : Author
Jonas Bybjerg-Grauholm
  • Function : Author
Na Cai
  • Function : Author
Enrique Castelao
  • Function : Author
Jane Hvarregaard Christensen
  • Function : Author
Toni-Kim Clarke
  • Function : Author
Jonathan R I Coleman
  • Function : Author
Lucía Colodro-Conde
  • Function : Author
Nick Craddock
  • Function : Author
Gregory E Crawford
  • Function : Author
Gail Davies
  • Function : Author
Ian J Deary
  • Function : Author
Franziska Degenhardt
  • Function : Author
Eske M Derks
  • Function : Author
Nese Direk
  • Function : Author
Conor V Dolan
  • Function : Author
Erin C Dunn
  • Function : Author
Thalia C Eley
  • Function : Author
Valentina Escott-Price
  • Function : Author
Farnush Farhadi Hassan Kiadeh
  • Function : Author
Hilary K Finucane
  • Function : Author
Andreas J Forstner
  • Function : Author
Josef Frank
  • Function : Author
Héléna A Gaspar
  • Function : Author
Michael Gill
  • Function : Author
Fernando S Goes
  • Function : Author
Scott D Gordon
  • Function : Author
Jakob Grove
  • Function : Author
Lynsey S Hall
  • Function : Author
Christine Søholm Hansen
  • Function : Author
Thomas F Hansen
  • Function : Author
Stefan Herms
  • Function : Author
Ian B Hickie
  • Function : Author
Per Hoffmann
  • Function : Author
Georg Homuth
  • Function : Author
Carsten Horn
  • Function : Author
Jouke-Jan Hottenga
  • Function : Author
David M Hougaard
  • Function : Author
Marcus Ising
  • Function : Author
Rick Jansen
  • Function : Author
Eric Jorgenson
  • Function : Author
James A Knowles
  • Function : Author
Isaac S Kohane
  • Function : Author
Julia Kraft
  • Function : Author
Warren W Kretzschmar
  • Function : Author
Jesper Krogh
  • Function : Author
Zoltán Kutalik
  • Function : Author
Yihan Li
  • Function : Author
Penelope A Lind
  • Function : Author
Donald J Macintyre
  • Function : Author
Dean F Mackinnon
  • Function : Author
Robert M Maier
  • Function : Author
Wolfgang Maier
  • Function : Author
Jonathan Marchini
  • Function : Author
Hamdi Mbarek
  • Function : Author
Patrick Mcgrath
  • Function : Author
Peter Mcguffin
  • Function : Author
Sarah E Medland
  • Function : Author
Divya Mehta
  • Function : Author
Christel M Middeldorp
  • Function : Author
Evelin Mihailov
  • Function : Author
Yuri Milaneschi
  • Function : Author
Lili Milani
  • Function : Author
Francis M Mondimore
  • Function : Author
Grant W Montgomery
  • Function : Author
Sara Mostafavi
  • Function : Author
Niamh Mullins
  • Function : Author
Matthias Nauck
  • Function : Author
Bernard Ng
  • Function : Author
Michel G Nivard
  • Function : Author
Dale R Nyholt
  • Function : Author
Paul F O’reilly
  • Function : Author
Hogni Oskarsson
  • Function : Author
Michael J Owen
  • Function : Author
Jodie N Painter
  • Function : Author
Carsten Bøcker Pedersen
  • Function : Author
Marianne Giørtz Pedersen
  • Function : Author
Roseann E Peterson
  • Function : Author
Erik Pettersson
  • Function : Author
Wouter J Peyrot
  • Function : Author
Giorgio Pistis
  • Function : Author
Danielle Posthuma
  • Function : Author
Jorge A Quiroz
  • Function : Author
Per Qvist
  • Function : Author
John P Rice
  • Function : Author
Brien P Riley
  • Function : Author
Margarita Rivera
  • Function : Author
Saira Saeed Mirza
  • Function : Author
Robert Schoevers
  • Function : Author
Eva C Schulte
  • Function : Author
Ling Shen
  • Function : Author
Jianxin Shi
  • Function : Author
Stanley I Shyn
  • Function : Author
Engilbert Sigurdsson
  • Function : Author
Grant C B Sinnamon
  • Function : Author
Johannes H Smit
  • Function : Author
Daniel J Smith
  • Function : Author
Hreinn Stefansson
  • Function : Author
Stacy Steinberg
  • Function : Author
Fabian Streit
  • Function : Author
Jana Strohmaier
  • Function : Author
Katherine E Tansey
  • Function : Author
Henning Teismann
  • Function : Author
Alexander Teumer
  • Function : Author
Wesley Thompson
  • Function : Author
Pippa A Thomson
  • Function : Author
Thorgeir E Thorgeirsson
  • Function : Author
Matthew Traylor
  • Function : Author
Jens Treutlein
  • Function : Author
Vassily Trubetskoy
  • Function : Author
André G Uitterlinden
  • Function : Author
Daniel Umbricht
  • Function : Author
Sandra van der Auwera
  • Function : Author
Albert M van Hemert
  • Function : Author
Alexander Viktorin
  • Function : Author
Peter M Visscher
  • Function : Author
Yunpeng Wang
  • Function : Author
Bradley T Webb
  • Function : Author
Shantel Marie Weinsheimer
  • Function : Author
Jürgen Wellmann
  • Function : Author
Gonneke Willemsen
  • Function : Author
Stephanie H Witt
  • Function : Author
Yang Wu
  • Function : Author
Hualin S Xi
  • Function : Author
Jian Yang
  • Function : Author
Futao Zhang
  • Function : Author
Volker Arolt
  • Function : Author
Bernhard T Baune
  • Function : Author
Klaus Berger
  • Function : Author
Dorret I Boomsma
  • Function : Author
Sven Cichon
  • Function : Author
Udo Dannlowski
  • Function : Author
E J C de Geus
  • Function : Author
J Raymond Depaulo
  • Function : Author
Enrico Domenici
  • Function : Author
Katharina Domschke
  • Function : Author
Tõnu Esko
  • Function : Author
Hans J Grabe
  • Function : Author
Steven P Hamilton
  • Function : Author
Caroline Hayward
  • Function : Author
Andrew C Heath
  • Function : Author
Kenneth S Kendler
  • Function : Author
Stefan Kloiber
  • Function : Author
Glyn Lewis
  • Function : Author
Qingqin S Li
  • Function : Author
Susanne Lucae
  • Function : Author
Pamela a F Madden
  • Function : Author
Patrik K Magnusson
  • Function : Author
Nicholas G Martin
  • Function : Author
Andrew M Mcintosh
  • Function : Author
Andres Metspalu
  • Function : Author
Ole Mors
  • Function : Author
Preben Bo Mortensen
  • Function : Author
Bertram Müller-Myhsok
  • Function : Author
Merete Nordentoft
  • Function : Author
Markus M Nöthen
  • Function : Author
Michael C O’donovan
  • Function : Author
Sara A Paciga
  • Function : Author
Nancy L Pedersen
  • Function : Author
Brenda W J H Penninx
  • Function : Author
Roy H Perlis
  • Function : Author
David J Porteous
  • Function : Author
James B Potash
  • Function : Author
Martin Preisig
  • Function : Author
Marcella Rietschel
  • Function : Author
Catherine Schaefer
  • Function : Author
Thomas G Schulze
  • Function : Author
Jordan W Smoller
  • Function : Author
Kari Stefansson
  • Function : Author
Henning Tiemeier
  • Function : Author
Rudolf Uher
  • Function : Author
Henry Völzke
  • Function : Author
Myrna M Weissman
  • Function : Author
Thomas Werge
  • Function : Author
Cathryn M Lewis
  • Function : Author
Douglas F Levinson
  • Function : Author
Gerome Breen
  • Function : Author
Anders D Børglum
  • Function : Author
Patrick F Sullivan
  • Function : Author
Katri Räikkönen
  • Function : Author

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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hal-04434844 , version 1 (02-02-2024)

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Darina Czamara, Gökçen Eraslan, Christian M Page, Jari Lahti, Marius Lahti-Pulkkinen, et al.. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications, 2019, 10, ⟨10.1038/s41467-019-10461-0⟩. ⟨hal-04434844⟩
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