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
Department of Translational Research in Psychiatry
Institute of Computational Biology
Helmholtz Zentrum München - German Research Center for Environmental Health
School of Life Sciences
Technical University of Munich
Oslo Centre for Biostatistics and Epidemiology
University of Oslo
Centre for Fertility and Health
Norwegian Institute of Public Health
Department of Psychology and Logopedics
University of Helsinki
University of Edinburgh
PEDEGO Research Unit
University of Oulu
Hospital District of Helsinki and Uusimaa
National Institute for Health and Welfare
Helsinki University Hospital
Institute for Molecular Genetics Finland
Faculty of Medicine and Life Sciences
Tampere University
Department of Obstetrics and Gynecology
Department of Chronic Diseases and Ageing
National Institutes of Health
Douglas Mental Health University Institute
McGill University
Agency for Science, Technology and Research, Singapore
corporate member of Freie Universität Berlin
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
Irvine
University of California at Irvine
Department of Psychiatry and Human Behavior
Centre for Molecular Medicine and Therapeutics
University of British Columbia
Department of Psychiatry and Mental Health
University of Cape Town
South African Medical Research Council
Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health
Department of Epidemiology
Harvard University
Department of Mathematics
Queensland Brain Institute
Analytic and Translational Genetics Unit
Massachusetts General Hospital
Department of Psychiatry and Psychotherapy
Charité – Universitätsmedizin Berlin
Medical and Population Genetics
Broad Institute
Karolinska Institutet
Department of Biomedicine
Aarhus University
iSEQ
iPSYCH
The Lundbeck Foundation Initiative for Integrative Psychiatric Research
University of Amsterdam
Division of Psychiatry
Centre for Integrated Register-based Research
National Centre for Register-Based Research
Discipline of Psychiatry
Adelaide University
Munich Cluster for Systems Neurology (SyNergy)
Virginia Commonwealth University
Center for Neonatal Screening
Statens Serum Institut
Department of Psychiatry
VU University Medical Center
Virginia Institute for Psychiatric and Behavior Genetics
Department of Medical Epidemiology and Biostatistics
Department of Clinical Medicine

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

113 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 - 11 Jun 2019
Externally published	Yes

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10.1038/s41467-019-10461-0

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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 = jun,

day = "11",

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

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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TY - JOUR

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 - 2019/6/11

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.

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

Abstract

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