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

Czamara, Darina, Eraslan, Goekcen, Page, Christian M., Lahti, Jari, Lahti-Pulkkinen, Marius, Hamalainen, Esa, Kajantie, Eero, Laivuori, Hannele, Villa, Pia M., Reynolds, Rebecca M., Nystad, Wenche, Haberg, Siri E., London, Stephanie J., O'Donnell, Kieran J., Garg, Elika, Meaney, Michael J., Entringer, Sonja, Wadhwa, Pathik D., Buss, Claudia, Jones, Meaghan J., Lin, David T.S., MacIsaac, Julie L., Kobor, Michael S., Koen, Nastassja, Zar, Heather J., Koenen, Karestan C., Dalvie, Shareefa, Stein, Dan J., Kondofersky, Ivan, Mueller, Nikola S., Theis, Fabian J., Raikkonen, Katri, Binder, Elisabeth B., Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F.M., Bacanu, Silviu-Alin, Baekvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Blackwood, Douglas H.R., Bryois, Julien, Buttenschon, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R., Colodro-Conde, Lucia, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor, Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Kiadeh, Farnush Farhadi Hassan, Finucane, Hilary K., Forstner, Andreas J., Frank, Josef, Gaspar, Helena A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Soholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Ising, Marcus, Jansen, Rick, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltan, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bocker, Pedersen, Marianne Girtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley, Sigurdsson, Engilbert, Sinnamon, Grant C.B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, Andre G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Weinsheimer, Shantel Marie, Wellmann, Juergen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret, Cichon, Sven, Dannlowski, Udo, de Geus, E.J.C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tonu, Grabe, Hans J., Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Mueller-Myhsok, Bertram, Nordentoft, Merete, Noethen, Markus M., O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Penninx, Brenda W.J.H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Voelzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Borglum, Anders D., and Sullivan, Patrick F. (2019) Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications, 10. 2548.

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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.

Item ID: 59961
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: © The Author(s) 2019.
Funders: Academy of Finland, University of Helsinki Research Funds, British Heart Foundation, Tommy’s, European Commission (EC), NorFace DIAL, Foundation for Pediatric Research, Juho Vainio Foundation, Novo Nordisk Foundation, Signe and Ane Gyllenberg Foundation, Sigrid Jusélius Foundation, Finnish Medical Foundation, Jane and Aatos Erkko Foundation, Päivikki and Sakari Sohlberg Foundation, Clinical Graduate school in Pediatrics and Obstetrics/Gynaecology in University of Helsinki, Norwegian Ministry of Health and Care Services and the Ministry of Education and Research (HCS & ER), National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS), Norwegian Research Council/BIOBANK (NRC), Research Council of Norway (RCN), Bill and Melinda Gates Foundation (BMGF), Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NICHD), Fogarty International Center, South African Medical Research Council (SAMRC), German Federal Ministry of Education and Research (BMBF), European Research Area Network (ERAN), Canadian Institute for Advanced Research (CIFAR)
Projects and Grants: EC Horizon 2020 Award SC1–2016-RTD-733280 RECAP, HCS & ER NIH/NIEHS contract no N01-ES-75558, NIH/NINDS grant no. 1 UO1 NS 047537–01 and grant no. 2 UO1 NS 047537–06A1, NIH Intramural Research Program, NIEHS Z01-ES-49019, NRC grant no 221097, RCN Centres of Excellence funding scheme, project number 262700, BMGF OPP 1017641, NICHD Award Number R21HD085849, SAMRC Self-Initiated Research Grant, BMBF Research Consortium Integrated Network IntegraMent, grant 01ZX1314H, ERAN Neuron grant 01EW1407A, CB, NIH grants R01 HD-060628 & R01 MH-105538, CIFAR Child and Brain Development Program
Date Deposited: 26 Jun 2019 07:33
FoR Codes: 06 BIOLOGICAL SCIENCES > 0604 Genetics > 060404 Epigenetics (incl Genome Methylation and Epigenomics) @ 100%
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