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., I; 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, V; 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, I; 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, I; 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.; Sullivan, Patrick F. (2019-06-11)
 
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URL:
https://doi.org/10.1038/s41467-019-10461-0

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., I
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, V
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, I
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, I
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.
Sullivan, Patrick F.
Springer Nature
11.06.2019

Czamara, D., Eraslan, G., Page, C.M. et al. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nat Commun 10, 2548 (2019). https://doi.org/10.1038/s41467-019-10461-0

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doi:https://doi.org/10.1038/s41467-019-10461-0
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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.

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