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

Darina Czamara, Gökçen Eraslan, Christian M. Page, Jari Lahti, Marius Lahti-Pulkkinen, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M. Villa, Rebecca M. Reynolds, Wenche Nystad, Siri E. Håberg, Stephanie J. London, Kieran J. O’Donnell, Elika Garg, Michael J. Meaney, Sonja Entringer, Pathik D. Wadhwa, Claudia Buss, Meaghan 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. Müller, Fabian J. Theis, Katri Räikkönen and Elisabeth B. Binder ()
Additional contact information
Darina Czamara: Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry
Gökçen 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 Hämäläinen: Helsinki University
Eero Kajantie: Oulu University Hospital and University of Oulu, PEDEGO Research Unit
Hannele Laivuori: Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital
Pia M. Villa: Medical and Clinical Genetics and Obstetrics and Gynaecology University of Helsinki and Helsinki University Central Hospital
Rebecca M. Reynolds: University of Edinburgh
Wenche Nystad: Norwegian Institute of Public Health
Siri E. Håberg: Norwegian Institute of Public Health
Stephanie J. London: Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services
Kieran J. O’Donnell: Douglas Mental Health University Institute, McGill University
Elika Garg: Douglas Mental Health University Institute, McGill University
Michael J. Meaney: Douglas Mental Health University Institute, McGill University
Sonja Entringer: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology
Pathik D. Wadhwa: University of California, Irvine, Development, Health, and Disease Research Program
Claudia Buss: Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Medical Psychology
Meaghan J. Jones: University of British Columbia and the BC Children’s Hospital Research Institute
David T. S. Lin: University of British Columbia and the BC Children’s Hospital Research Institute
Julie L. MacIsaac: University of British Columbia and the BC Children’s Hospital Research Institute
Michael S. Kobor: University of British Columbia and the BC Children’s Hospital Research Institute
Nastassja Koen: University of Cape Town
Heather J. Zar: University of Cape Town
Karestan C. Koenen: Harvard T. H. 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. Müller: German Research Center for Environmental Health
Fabian J. Theis: German Research Center for Environmental Health
Katri Räikkönen: University of Helsinki
Elisabeth B. Binder: Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10461-0

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