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; Naomi R. Wray; Stephan Ripke; Manuel Mattheisen; Maciej Trzaskowski; Enda M. Byrne; Abdel Abdellaoui; Mark J. Adams; Esben Agerbo; Tracy M. Air; Till F. M. Andlauer; Silviu-Alin Bacanu; Marie Bækvad-Hansen; Aartjan T. F. Beekman; Tim B. Bigdeli; Douglas H. R. Blackwood; Julien Bryois; Henriette N. Buttenschøn; Jonas Bybjerg-Grauholm; Na Cai; Enrique Castelao; Jane Hvarregaard Christensen; Toni-Kim Clarke; Jonathan R. I. Coleman; Lucía Colodro-Conde; Baptiste Couvy-Duchesne; Nick Craddock; Gregory E. Crawford; Gail Davies; Ian J. Deary; Franziska Degenhardt; Eske M. Derks; Nese Direk; Conor V. 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 F. Hansen; Stefan Herms; Ian B. Hickie; Per Hoffmann; Georg Homuth; Carsten Horn; Jouke-Jan Hottenga; David M. Hougaard; Marcus Ising; Rick 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; Dean F. MacKinnon; Robert M. Maier; Wolfgang Maier; Jonathan Marchini; Hamdi Mbarek; Patrick McGrath; Peter McGuffin; Sarah E. Medland; Divya Mehta; Christel M. Middeldorp; Evelin Mihailov; Yuri Milaneschi; Lili Milani; Francis M. Mondimore; Grant W. Montgomery; Sara Mostafavi; Niamh Mullins; Matthias Nauck; Bernard Ng; Michel G. Nivard; Dale R. Nyholt; Paul F. O’Reilly; Hogni Oskarsson; Michael J. Owen; Jodie N. Painter; Carsten Bøcker Pedersen; Marianne Giørtz Pedersen; Roseann E. Peterson; Erik Pettersson; Wouter J. Peyrot; Giorgio Pistis; Danielle Posthuma; Jorge A. Quiroz; Per Qvist; John P. Rice; Brien P. Riley; Margarita Rivera; Saira Saeed Mirza; Robert Schoevers; Eva C. Schulte; Ling Shen; Jianxin Shi; Stanley I. Shyn; Engilbert Sigurdsson; Grant C. B. Sinnamon; Johannes H. Smit; Daniel J. Smith; Hreinn Stefansson; Stacy Steinberg; Fabian Streit; Jana Strohmaier; Katherine E. Tansey; Henning Teismann; Alexander Teumer; Wesley Thompson; Pippa A. Thomson; Thorgeir E. Thorgeirsson; Matthew Traylor; Jens Treutlein; Vassily Trubetskoy; André G. Uitterlinden; Daniel Umbricht; Sandra Van der Auwera; Albert M. van Hemert; Alexander Viktorin; Peter M. Visscher; Yunpeng Wang; Bradley T. Webb; Shantel Marie Weinsheimer; Jürgen Wellmann; Gonneke Willemsen; Stephanie H. Witt; Yang Wu; Hualin S. Xi; Jian Yang; Futao Zhang; Volker Arolt; Bernhard T. Baune; Klaus Berger; Dorret I. Boomsma; Sven Cichon; Udo Dannlowski; E. J. C. de Geus; J. Raymond DePaulo; Enrico Domenici; Katharina Domschke; Tõnu Esko; Hans J. Grabe; Steven P. Hamilton; Caroline Hayward; Andrew C. Heath; Kenneth S. Kendler; Stefan Kloiber; Glyn Lewis; Qingqin S. Li; Susanne Lucae; Pamela A. F. Madden; Patrik K. Magnusson; Nicholas G. Martin; Andrew M. McIntosh; Andres Metspalu; Ole Mors; Preben Bo Mortensen; Bertram Müller-Myhsok; Merete Nordentoft; Markus M. Nöthen; Michael C. O’Donovan; Sara A. Paciga; Nancy L. Pedersen; Brenda W. J. H. Penninx; Roy H. Perlis; David J. Porteous; James B. Potash; Martin Preisig; Marcella Rietschel; Catherine Schaefer; Thomas G. Schulze; Jordan W. Smoller; Kari Stefansson; Henning Tiemeier; Rudolf Uher; Henry Völzke; Myrna M. Weissman; Thomas Werge; Cathryn M. Lewis; Douglas F. Levinson; Gerome Breen; Anders D. Børglum; Patrick F. Sullivan; Katri Räikkönen; Elisabeth B. Binder; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41467-019-10461-0

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. JonesDavid 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, Naomi R. Wray, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy M. Air, Till F. M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T. F. Beekman, Tim B. Bigdeli, Douglas H. R. Blackwood, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Toni-Kim Clarke, Jonathan R. I. Coleman, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Ian J. Deary, Franziska Degenhardt, Eske M. Derks, Nese Direk, Conor V. 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 F. Hansen, Stefan Herms, Ian B. Hickie, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, Marcus Ising, Rick 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, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Peter McGuffin, Sarah E. Medland, Divya Mehta, Christel M. Middeldorp, Evelin Mihailov, Yuri Milaneschi, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Niamh Mullins, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Michael J. Owen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Erik Pettersson, Wouter J. Peyrot, Giorgio Pistis, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Margarita Rivera, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Jianxin Shi, Stanley I. Shyn, Engilbert Sigurdsson, Grant C. B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Hreinn Stefansson, Stacy Steinberg, Fabian Streit, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Sandra Van der Auwera, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Stephanie H. Witt, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Sven Cichon, Udo Dannlowski, E. J. C. de Geus, J. Raymond DePaulo, Enrico Domenici, Katharina Domschke, Tõnu Esko, Hans J. Grabe, Steven P. Hamilton, Caroline Hayward, Andrew C. Heath, Kenneth S. Kendler, Stefan Kloiber, Glyn Lewis, Qingqin S. Li, Susanne Lucae, Pamela A. F. Madden, Patrik K. Magnusson, Nicholas G. Martin, Andrew M. McIntosh, Andres Metspalu, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Sara A. Paciga, Nancy L. Pedersen, Brenda W. J. H. Penninx, Roy H. Perlis, David J. Porteous, James B. Potash, Martin Preisig, Marcella Rietschel, Catherine Schaefer, Thomas G. Schulze, Jordan W. Smoller, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Henry Völzke, Myrna M. Weissman, Thomas Werge, Cathryn M. Lewis, Douglas F. Levinson, Gerome Breen, Anders D. Børglum, Patrick F. Sullivan, Katri Räikkönen, Elisabeth B. Binder, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Article number	2548
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-10461-0
Publication status	Published - 11 Jun 2019

Keywords / Materials (for Non-textual outputs)

biomarkers
DNA methylation
epigenomics

Access to Document

10.1038/s41467-019-10461-0Licence: Creative Commons: Attribution (CC-BY)

CzamaraEtalNC2019IntegratedAnalysisofEnvironmentalAndGeneticFinal published version, 1.06 MBLicence: Creative Commons: Attribution (CC-BY)

Stratifying Resilience and Depression Longitudinally
McIntosh, A., Deary, I., Evans, K., Haley, C. & Porteous, D.
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Project: Research

Cite this

Czamara, D., Eraslan, G., Page, C. M., Lahti, J., Lahti-Pulkkinen, M., Hämäläinen, E., Kajantie, E., Laivuori, H., Villa, P. M., Reynolds, R. M., Nystad, W., Håberg, S. E., London, S. J., O’Donnell, K. J., Garg, E., Meaney, M. J., Entringer, S., Wadhwa, P. D., Buss, C., ... Consortium, M. D. D. W. G. O. T. P. G. (2019). Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications, 10(1), Article 2548 . https://doi.org/10.1038/s41467-019-10461-0

@article{5b75fb2e5c554341bd74689c6c812d76,

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

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{\textquoteright}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.",

keywords = "biomarkers, DNA methylation, epigenomics",

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

year = "2019",

month = jun,

day = "11",

doi = "10.1038/s41467-019-10461-0",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Czamara, D, Eraslan, G, Page, CM, Lahti, J, Lahti-Pulkkinen, M, Hämäläinen, E, Kajantie, E, Laivuori, H, Villa, PM, Reynolds, RM, Nystad, W, Håberg, SE, London, SJ, O’Donnell, KJ, Garg, E, Meaney, MJ, Entringer, S, Wadhwa, PD, Buss, C, Jones, MJ, Lin, DTS, MacIsaac, JL, Kobor, MS, Koen, N, Zar, HJ, Koenen, KC, Dalvie, S, Stein, DJ, Kondofersky, I, Müller, NS, Theis, FJ, Wray, NR, Ripke, S, Mattheisen, M, Trzaskowski, M, Byrne, EM, Abdellaoui, A, Adams, MJ, Agerbo, E, Air, TM, Andlauer, TFM, Bacanu, S-A, Bækvad-Hansen, M, Beekman, ATF, Bigdeli, TB, Blackwood, DHR, Bryois, J, Buttenschøn, HN, Bybjerg-Grauholm, J, Cai, N, Castelao, E, Christensen, JH, Clarke, T-K, Coleman, JRI, Colodro-Conde, L, Couvy-Duchesne, B, Craddock, N, Crawford, GE, Davies, G , Deary, IJ, Degenhardt, F, Derks, EM, Direk, N, Dolan, CV, Dunn, EC, Eley, TC, Escott-Price, V, Kiadeh, FFH, Finucane, HK, Forstner, AJ, Frank, J, Gaspar, HA, Gill, M, Goes, FS, Gordon, SD, Grove, J, Hall, LS, Hansen, CS, Hansen, TF, Herms, S, Hickie, IB, Hoffmann, P, Homuth, G, Horn, C, Hottenga, J-J, Hougaard, DM, Ising, M, Jansen, R, Jorgenson, E, Knowles, JA, Kohane, IS, Kraft, J, Kretzschmar, WW, Krogh, J, Kutalik, Z, Li, Y, Lind, PA, MacIntyre, DJ, MacKinnon, DF, Maier, RM, Maier, W, Marchini, J, Mbarek, H, McGrath, P, McGuffin, P, Medland, SE, Mehta, D, Middeldorp, CM, Mihailov, E, Milaneschi, Y, Milani, L, Mondimore, FM, Montgomery, GW, Mostafavi, S, Mullins, N, Nauck, M, Ng, B, Nivard, MG, Nyholt, DR, O’Reilly, PF, Oskarsson, H, Owen, MJ, Painter, JN, Pedersen, CB, Pedersen, MG, Peterson, RE, Pettersson, E, Peyrot, WJ, Pistis, G, Posthuma, D, Quiroz, JA, Qvist, P, Rice, JP, Riley, BP, Rivera, M, Mirza, SS, Schoevers, R, Schulte, EC, Shen, L, Shi, J, Shyn, SI, Sigurdsson, E, Sinnamon, GCB, Smit, JH, Smith, DJ, Stefansson, H, Steinberg, S, Streit, F, Strohmaier, J, Tansey, KE, Teismann, H, Teumer, A, Thompson, W, Thomson, PA, Thorgeirsson, TE, Traylor, M, Treutlein, J, Trubetskoy, V, Uitterlinden, AG, Umbricht, D, Van der Auwera, S, van Hemert, AM, Viktorin, A, Visscher, PM, Wang, Y, Webb, BT, Weinsheimer, SM, Wellmann, J, Willemsen, G, Witt, SH, Wu, Y, Xi, HS, Yang, J, Zhang, F, Arolt, V, Baune, BT, Berger, K, Boomsma, DI, Cichon, S, Dannlowski, U, de Geus, EJC, DePaulo, JR, Domenici, E, Domschke, K, Esko, T, Grabe, HJ, Hamilton, SP, Hayward, C, Heath, AC, Kendler, KS, Kloiber, S, Lewis, G, Li, QS, Lucae, S, Madden, PAF, Magnusson, PK, Martin, NG, McIntosh, AM, Metspalu, A, Mors, O, Mortensen, PB, Müller-Myhsok, B, Nordentoft, M, Nöthen, MM, O’Donovan, MC, Paciga, SA, Pedersen, NL, Penninx, BWJH, Perlis, RH, Porteous, DJ, Potash, JB, Preisig, M, Rietschel, M, Schaefer, C, Schulze, TG, Smoller, JW, Stefansson, K, Tiemeier, H, Uher, R, Völzke, H, Weissman, MM, Werge, T, Lewis, CM, Levinson, DF, Breen, G, Børglum, AD, Sullivan, PF, Räikkönen, K, Binder, EB & Consortium, MDDWGOTPG 2019, 'Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns', Nature Communications, vol. 10, no. 1, 2548 . https://doi.org/10.1038/s41467-019-10461-0

TY - JOUR

T1 - Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

AU - Czamara, Darina

AU - Eraslan, Gökçen

AU - Page, Christian M.

AU - Lahti, Jari

AU - Lahti-Pulkkinen, Marius

AU - Hämäläinen, Esa

AU - Kajantie, Eero

AU - Laivuori, Hannele

AU - Villa, Pia M.

AU - Reynolds, Rebecca M.

AU - Nystad, Wenche

AU - Håberg, Siri E.

AU - London, Stephanie J.

AU - O’Donnell, Kieran J.

AU - Garg, Elika

AU - Meaney, Michael J.

AU - Entringer, Sonja

AU - Wadhwa, Pathik D.

AU - Buss, Claudia

AU - Jones, Meaghan J.

AU - Lin, David T. S.

AU - MacIsaac, Julie L.

AU - Kobor, Michael S.

AU - Koen, Nastassja

AU - Zar, Heather J.

AU - Koenen, Karestan C.

AU - Dalvie, Shareefa

AU - Stein, Dan J.

AU - Kondofersky, Ivan

AU - Müller, Nikola S.

AU - Theis, Fabian J.

AU - Wray, Naomi R.

AU - Ripke, Stephan

AU - Mattheisen, Manuel

AU - Trzaskowski, Maciej

AU - Byrne, Enda M.

AU - Abdellaoui, Abdel

AU - Adams, Mark J.

AU - Agerbo, Esben

AU - Air, Tracy M.

AU - Andlauer, Till F. M.

AU - Bacanu, Silviu-Alin

AU - Bækvad-Hansen, Marie

AU - Beekman, Aartjan T. F.

AU - Bigdeli, Tim B.

AU - Blackwood, Douglas H. R.

AU - Bryois, Julien

AU - Buttenschøn, Henriette N.

AU - Bybjerg-Grauholm, Jonas

AU - Cai, Na

AU - Castelao, Enrique

AU - Christensen, Jane Hvarregaard

AU - Clarke, Toni-Kim

AU - Coleman, Jonathan R. I.

AU - Colodro-Conde, Lucía

AU - Couvy-Duchesne, Baptiste

AU - Craddock, Nick

AU - Crawford, Gregory E.

AU - Davies, Gail

AU - Deary, Ian J.

AU - Degenhardt, Franziska

AU - Derks, Eske M.

AU - Direk, Nese

AU - Dolan, Conor V.

AU - Dunn, Erin C.

AU - Eley, Thalia C.

AU - Escott-Price, Valentina

AU - Kiadeh, Farnush Farhadi Hassan

AU - Finucane, Hilary K.

AU - Forstner, Andreas J.

AU - Frank, Josef

AU - Gaspar, Héléna A.

AU - Gill, Michael

AU - Goes, Fernando S.

AU - Gordon, Scott D.

AU - Grove, Jakob

AU - Hall, Lynsey S.

AU - Hansen, Christine Søholm

AU - Hansen, Thomas F.

AU - Herms, Stefan

AU - Hickie, Ian B.

AU - Hoffmann, Per

AU - Homuth, Georg

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AU - Binder, Elisabeth B.

AU - Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics

PY - 2019/6/11

Y1 - 2019/6/11

N2 - 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.

AB - 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.

KW - biomarkers

KW - DNA methylation

KW - epigenomics

U2 - 10.1038/s41467-019-10461-0

DO - 10.1038/s41467-019-10461-0

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2548

ER -

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

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Stratifying Resilience and Depression Longitudinally

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