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

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Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ; Werge, Thomas Mears ; Hansen, Thomas Folkmann. / Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. In: Nature Communications. 2019 ; Vol. 10, No. 1. pp. 2548.

Bibtex

@article{eb1975d8a21c434f92950633ed732187,
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'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.",
keywords = "Cohort Studies, DNA/blood, DNA Methylation/genetics, Epigenesis, Genetic, Female, Fetal Blood, Gene-Environment Interaction, Genotype, Humans, Infant, Newborn, Male, Pregnancy, Risk Factors",
author = "Darina Czamara and G{\"o}k{\cc}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'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 Katri R{\"a}ikk{\"o}nen and Binder, {Elisabeth B} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Werge, {Thomas Mears} and Hansen, {Thomas Folkmann}",
year = "2019",
month = "6",
day = "11",
doi = "10.1038/s41467-019-10461-0",
language = "English",
volume = "10",
pages = "2548",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

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 - Räikkönen, Katri

AU - Binder, Elisabeth B

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

AU - Hansen, Thomas Folkmann

A2 - Werge, Thomas Mears

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.

KW - Cohort Studies

KW - DNA/blood

KW - DNA Methylation/genetics

KW - Epigenesis, Genetic

KW - Female

KW - Fetal Blood

KW - Gene-Environment Interaction

KW - Genotype

KW - Humans

KW - Infant, Newborn

KW - Male

KW - Pregnancy

KW - Risk Factors

U2 - 10.1038/s41467-019-10461-0

DO - 10.1038/s41467-019-10461-0

M3 - Journal article

VL - 10

SP - 2548

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -

ID: 59084457