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

doi: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

Institute for Molecular Bioscience
University of Queensland
Max Planck Institute of Psychiatry
Helmholtz Zentrum München - German Research Center for Environmental Health
Technical University of Munich
University of Oslo
Norwegian Institute of Public Health
University of Helsinki
University of Edinburgh
University of Oulu
Hospital District of Helsinki and Uusimaa
National Institute for Health and Welfare
Helsinki University Hospital
Tampere University
National Institutes of Health
Douglas Mental Health University Institute
McGill University
Agency for Science, Technology and Research, Singapore
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
University of California at Irvine
University of British Columbia
University of Cape Town
South African Medical Research Council
Harvard University
Massachusetts General Hospital
Charité – Universitätsmedizin Berlin
Broad Institute
Karolinska Institutet
Aarhus University
The Lundbeck Foundation Initiative for Integrative Psychiatric Research
University of Amsterdam
Adelaide University
Munich Cluster for Systems Neurology (SyNergy)
Virginia Commonwealth University
Statens Serum Institut
VU University Medical Center
Virginia Institute for Psychiatric and Behavior Genetics
Wellcome Trust Sanger Institute
European Molecular Biology Laboratory
University of Lausanne
King's College London
Queensland Institute of Medical Research
Cardiff University
Duke University
University of Bonn
Erasmus University Rotterdam
Dokuz Eylul University
Massachusetts Institute of Technology
University of Basel
Heidelberg University
Trinity College Dublin
Johns Hopkins University
Newcastle University
University of Copenhagen
Mental Health Services Capital Region of Denmark
H. Lundbeck A/S
The University of Sydney
University of Greifswald
F. Hoffmann-La Roche AG
Kaiser Permanente
University of Southern California
Brigham and Women’s Hospital
Boston Children's Hospital
University of Oxford
Swiss Institute of Bioinformatics
National Health Service Scotland
Columbia University
Queensland University of Technology
Children’s Health Queensland
University of Tartu
German Centre for Cardiovascular Research
Humus Inc
Vrije Universiteit Amsterdam
Solid Biosciences
Washington University St. Louis
University of Granada
University of Groningen
Ludwig Maximilian University of Munich
University of Iceland
James Cook University Queensland
University of Glasgow
deCODE Genetics
University of Münster
University of California at San Diego
University of Cambridge
Leiden University
Pfizer
Jülich Research Centre
University of Trento
University of Freiburg
University of Toronto
University College London
Johnson & Johnson
University of Tartu
University of Liverpool
University of Iowa
University of Göttingen
Dalhousie University
Stanford University
University of North Carolina at Chapel Hill
Emory University

Research output: Contribution to journal › Article › peer-review

105 Citations (Scopus)

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
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10461-0
Publication status	Published - 1 Dec 2019
Externally published	Yes

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@article{684be05a5ce940ec8f80400fcc8f4a37,

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

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{\textquoteright}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.",

author = "\{Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium\} and Darina Czamara and G{\"o}k{\c c}en Eraslan and Page, \{Christian M.\} and Jari Lahti and Marius Lahti-Pulkkinen and Esa H{\"a}m{\"a}l{\"a}inen and Eero Kajantie and Hannele Laivuori and Villa, \{Pia M.\} and Reynolds, \{Rebecca M.\} and Wenche Nystad and H{\aa}berg, \{Siri E.\} and London, \{Stephanie J.\} and O{\textquoteright}Donnell, \{Kieran J.\} and Elika Garg and Meaney, \{Michael J.\} and Sonja Entringer and Wadhwa, \{Pathik D.\} and Claudia Buss and Jones, \{Meaghan J.\} and Lin, \{David T.S.\} and MacIsaac, \{Julie L.\} and Kobor, \{Michael S.\} and Nastassja Koen and Zar, \{Heather J.\} and Koenen, \{Karestan C.\} and Shareefa Dalvie and Stein, \{Dan J.\} and Ivan Kondofersky and M{\"u}ller, \{Nikola S.\} and Theis, \{Fabian J.\} and Wray, \{Naomi R.\} and Stephan Ripke and Manuel Mattheisen and Maciej Trzaskowski and Byrne, \{Enda M.\} and Abdel Abdellaoui and Adams, \{Mark J.\} and Esben Agerbo and Air, \{Tracy M.\} and Andlauer, \{Till F.M.\} and Bacanu, \{Silviu Alin\} and Marie B{\ae}kvad-Hansen and Beekman, \{Aartjan T.F.\} and Bigdeli, \{Tim B.\} and Blackwood, \{Douglas H.R.\} and Julien Bryois and Buttensch{\o}n, \{Henriette N.\} and Jonas Bybjerg-Grauholm and Hottenga, \{Jouke Jan\}",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

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

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

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

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

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 - Hottenga, Jouke Jan

PY - 2019/12/1

Y1 - 2019/12/1

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.

UR - https://www.scopus.com/pages/publications/85067229888

U2 - 10.1038/s41467-019-10461-0

DO - 10.1038/s41467-019-10461-0

M3 - Article

C2 - 31186427

AN - SCOPUS:85067229888

SN - 2041-1723

VL - 10

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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