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

Psychiat Genomics Consortium, Darina Czamara, Goekcen Eraslan, Christian M. Page, Jari Lahti, Marius Lahti-Pulkkinen, Esa Hamalainen, Eero Kajantie, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Wenche Nystad, Siri E. Haberg, Stephanie J. London, Kieran J. O'Donnell, Elika Garg, Michael J. Meaney, Sonja Entringer, Pathik D. Wadhwa, Claudia BussMeaghan 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. Mueller, Fabian J. Theis, Katri Raikkonen, Elisabeth B. Binder*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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
Article number2548
Number of pages18
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 11-Jun-2019

Keywords

  • CHILDHOOD MALTREATMENT
  • NORWEGIAN MOTHER
  • MATERNAL SMOKING
  • PRENATAL STRESS
  • GENOME-WIDE
  • IN-UTERO
  • PREGNANCY
  • RISK
  • BIRTH
  • GENOTYPE

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