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 journalArticle

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 (US)
Article number2548
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 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

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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, No. 1, 2548, 01.12.2019.

Research output: Contribution to journalArticle

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, no. 1, 2548. https://doi.org/10.1038/s41467-019-10461-0
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, No. 1.
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