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

• Type of Material: Article
• Authors: Darina Czamara, Max-Planck-Institute of Psychiatry; Gokcen Eraslan, German Research Center for Environmental Health; Christian M. Page, Oslo University Hospital; Jari Lahti, University of Helsinki; Marius Lahti-Pulkkinen, University of Helsinki; Esa Hamalainen, University of Helsinki; Eero Kajantie, Oulu University; Hannele Laivuori, University of Helsinki; Pia M. Villa, University of Helsinki; Rebecca M. Reynolds, University of Edinburgh; Wenche Nystad, Norwegian Institute of Public Health; Siri E. Haberg, Norwegian Institute of Public Health; Stephanie J London, National Institute of Environmental Health Sciences; Kieran J. O'Donnell, McGill University; Elika Garg, McGill University; Michael J. Meaney, McGill University; Sonja Entringer, Charite Medical University of Berlin; Pathik D. Wadhwa, University of California Irvine; Claudia Buss, Charite Medical University of Berlin; Meaghan J. Jones, University of British Columbia; David T.S. Lin, University of British Columbia; Julie L. MacIsaac, University of British Columbia; Michael S. Kobor, University of British Columbia; Nastassja Koen, University of Cape Town; Heather J. Zar, University of Cape Town; Karestan C. Koenen, Harvard TH Chan School of Public Health; Shareefa Dalvie, University of Cape Town; Dan J. Stein, University of Cape Town; Ivan Kondofersky, German Research Center for Environmental Health; Nikola S. Mueller, German Research Center for Environmental Health; Fabian J. Theis, German Research Center for Environmental Health; Katri Raikkonen, University of Helsinki; Elisabeth Binder, Emory University
• Language: English
• Date: 2019-06-11
• Publisher: Nature Research (part of Springer Nature): Fully open access journals
• Publication Version: Final Published Version
• Copyright Statement: © 2019, The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-019-10461-0
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 10
• Issue: 1
• Start Page: 2548
• End Page: 2548
• Keywords: GENOTYPE; Multidisciplinary Sciences; IN-UTERO; PREGNANCY; NORWEGIAN MOTHER; RISK; Science & Technology; MATERNAL SMOKING; PRENATAL STRESS; GENOME-WIDE; BIRTH; Science & Technology - Other Topics; CHILDHOOD MALTREATMENT
• Research Categories: Biology, Genetics; Health Sciences, Obstetrics and Gynecology; Psychology, Developmental

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.