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✓ Immediate verification • ✓ Free institutional access • ✓ Global collaborationEpigenetic 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.
Darina Czamara, Goekcen Eraslan, Christian M. Page, Jari Lahti, Marius Lahti‐Pulkkinen, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia 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 Lin, Julie L. MacIsaac, Michael S. Kobor, Nastassja Koen, Heather J. Zar, Karestan C. Koenen, Shareefa Dalvie, Dan Joseph Stein, Ivan Kondofersky, Nikola S. Mueller, Fabian J. Theis, Katri Räikkönen, Elisabeth B. Binder, Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy Air, Till F. M. Andlauer, Silviu‐Alin Bacanu, Marie Bækvad‐Hansen, Aartjan T.F. Beekman, Tim B. Bigdeli, Douglas Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg‐Grauholm, Na Cai, Enrique Castelao, Jane Christensen, Toni‐Kim Clarke, Jonathan R. Coleman, Lucía Colodro‐Conde, Baptiste Couvy‐Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Neşe Direk, Conor Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott‐Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Andreas J. Forstner, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke‐Jan Hottenga, David M. Hougaard, Marcus Ising, Philip R. Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Jesper Krogh, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre (2019). Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.
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Type
Article
Year
2019
Authors
100
Datasets
0
Total Files
0
Language
en
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