Plate IV.353 · Publications
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Article in Nature Communications, 11 June 2019.
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.
Versions2
- PublishedNature Communications10.1038/s41467-019-10461-0
- PreprintbioRxiv10.1101/436113
Cite
@article{czamara2019integrated,
title = {{Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns}},
author = {Czamara, Darina and Eraslan, Gökçen and Page, Christian M. and Lahti, Jari and Lahti-Pulkkinen, Marius and Hämäläinen, Esa and Kajantie, Eero and Laivuori, Hannele and Villa, Pia M. and Reynolds, Rebecca M. and Nystad, Wenche and Håberg, Siri E. and London, Stephanie J. and O’Donnell, Kieran J. and Garg, Elika and Meaney, Michael J. and Entringer, Sonja and Wadhwa, Pathik D. and Buss, Claudia and Jones, Meaghan J. and Lin, David T. S. and MacIsaac, Julie L. and Kobor, Michael S. and Koen, Nastassja and Zar, Heather J. and Koenen, Karestan C. and Dalvie, Shareefa and Stein, Dan J. and Kondofersky, Ivan and Müller, Nikola S. and Theis, Fabian J. and Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium and Wray, Naomi R. and Ripke, Stephan and Mattheisen, Manuel and Trzaskowski, Maciej and Byrne, Enda M. and Abdellaoui, Abdel and Adams, Mark J. and Agerbo, Esben and Air, Tracy M. and Andlauer, Till F. M. and Bacanu, Silviu-Alin and Bækvad-Hansen, Marie and Beekman, Aartjan T. F. and Bigdeli, Tim B. and Blackwood, Douglas H. R. and Bryois, Julien and Buttenschøn, Henriette N. and Bybjerg-Grauholm, Jonas and Cai, Na and Castelao, Enrique and Christensen, Jane Hvarregaard and Clarke, Toni-Kim and Coleman, Jonathan R. I. and Colodro-Conde, Lucía and Couvy-Duchesne, Baptiste and Craddock, Nick and Crawford, Gregory E. and Davies, Gail and Deary, Ian J. and Degenhardt, Franziska and Derks, Eske M. and Direk, Nese and Dolan, Conor V. and Dunn, Erin C. and Eley, Thalia C. and Escott-Price, Valentina and Kiadeh, Farnush Farhadi Hassan and Finucane, Hilary K. and Forstner, Andreas J. and Frank, Josef and Gaspar, Héléna A. and Gill, Michael and Goes, Fernando S. and Gordon, Scott D. and Grove, Jakob and Hall, Lynsey S. and Hansen, Christine Søholm and Hansen, Thomas F. and Herms, Stefan and Hickie, Ian B. and Hoffmann, Per and Homuth, Georg and Horn, Carsten and Hottenga, Jouke-Jan and Hougaard, David M. and Ising, Marcus and Jansen, Rick and Jorgenson, Eric and Knowles, James A. and Kohane, Isaac S. and Kraft, Julia and Kretzschmar, Warren W. and Krogh, Jesper and Kutalik, Zoltán and Li, Yihan and Lind, Penelope A. and MacIntyre, Donald J. and MacKinnon, Dean F. and Maier, Robert M. and Maier, Wolfgang and Marchini, Jonathan and Mbarek, Hamdi and McGrath, Patrick and McGuffin, Peter and Medland, Sarah E. and Mehta, Divya and Middeldorp, Christel M. and Mihailov, Evelin and Milaneschi, Yuri and Milani, Lili and Mondimore, Francis M. and Montgomery, Grant W. and Mostafavi, Sara and Mullins, Niamh and Nauck, Matthias and Ng, Bernard and Nivard, Michel G. and Nyholt, Dale R. and O’Reilly, Paul F. and Oskarsson, Hogni and Owen, Michael J. and Painter, Jodie N. and Pedersen, Carsten Bøcker and Pedersen, Marianne Giørtz and Peterson, Roseann E. and Pettersson, Erik and Peyrot, Wouter J. and Pistis, Giorgio and Posthuma, Danielle and Quiroz, Jorge A. and Qvist, Per and Rice, John P. and Riley, Brien P. and Rivera, Margarita and Mirza, Saira Saeed and Schoevers, Robert and Schulte, Eva C. and Shen, Ling and Shi, Jianxin and Shyn, Stanley I. and Sigurdsson, Engilbert and Sinnamon, Grant C. B. and Smit, Johannes H. and Smith, Daniel J. and Stefansson, Hreinn and Steinberg, Stacy and Streit, Fabian and Strohmaier, Jana and Tansey, Katherine E. and Teismann, Henning and Teumer, Alexander and Thompson, Wesley and Thomson, Pippa A. and Thorgeirsson, Thorgeir E. and Traylor, Matthew and Treutlein, Jens and Trubetskoy, Vassily and Uitterlinden, André G. and Umbricht, Daniel and Van der Auwera, Sandra and van Hemert, Albert M. and Viktorin, Alexander and Visscher, Peter M. and Wang, Yunpeng and Webb, Bradley T. and Weinsheimer, Shantel Marie and Wellmann, Jürgen and Willemsen, Gonneke and Witt, Stephanie H. and Wu, Yang and Xi, Hualin S. and Yang, Jian and Zhang, Futao and Arolt, Volker and Baune, Bernhard T. and Berger, Klaus and Boomsma, Dorret I. and Cichon, Sven and Dannlowski, Udo and de Geus, E. J. C. and DePaulo, J. Raymond and Domenici, Enrico and Domschke, Katharina and Esko, Tõnu and Grabe, Hans J. and Hamilton, Steven P. and Hayward, Caroline and Heath, Andrew C. and Kendler, Kenneth S. and Kloiber, Stefan and Lewis, Glyn and Li, Qingqin S. and Lucae, Susanne and Madden, Pamela A. F. and Magnusson, Patrik K. and Martin, Nicholas G. and McIntosh, Andrew M. and Metspalu, Andres and Mors, Ole and Mortensen, Preben Bo and Müller-Myhsok, Bertram and Nordentoft, Merete and Nöthen, Markus M. and O’Donovan, Michael C. and Paciga, Sara A. and Pedersen, Nancy L. and Penninx, Brenda W. J. H. and Perlis, Roy H. and Porteous, David J. and Potash, James B. and Preisig, Martin and Rietschel, Marcella and Schaefer, Catherine and Schulze, Thomas G. and Smoller, Jordan W. and Stefansson, Kari and Tiemeier, Henning and Uher, Rudolf and Völzke, Henry and Weissman, Myrna M. and Werge, Thomas and Lewis, Cathryn M. and Levinson, Douglas F. and Breen, Gerome and Børglum, Anders D. and Sullivan, Patrick F. and Räikkönen, Katri and Binder, Elisabeth B.},
journal = {Nature Communications},
publisher = {Springer Science and Business Media LLC},
year = {2019},
month = jun,
doi = {10.1038/s41467-019-10461-0},
url = {https://doi.org/10.1038/s41467-019-10461-0},
pmid = {31186427},
pmcid = {PMC6559955}
}