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.

Open accessResearch area: Diabetes, Children, Risk

Authors

  1. Darina Czamara
  2. Gökçen Eraslan
  3. Christian M. Page
  4. Jari Lahti
  5. Marius Lahti-Pulkkinen
  6. Esa Hämäläinen
  7. Eero Kajantie
  8. Hannele Laivuori
  9. Pia M. Villa
  10. Rebecca M. Reynolds
  11. Wenche Nystad
  12. Siri E. Håberg
  13. Stephanie J. London
  14. Kieran J. O’Donnell
  15. Elika Garg
  16. Michael J. Meaney
  17. Sonja Entringer
  18. Pathik D. Wadhwa
  19. Claudia Buss
  20. Meaghan J. Jones
  21. David T. S. Lin
  22. Julie L. MacIsaac
  23. Michael S. Kobor
  24. Nastassja Koen
  25. Heather J. Zar
  26. Karestan C. Koenen
  27. Shareefa Dalvie
  28. Dan J. Stein
  29. Ivan Kondofersky
  30. Nikola S. Müller
  31. Fabian J. Theis
  32. Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
  33. Naomi R. Wray
  34. Stephan Ripke
  35. Manuel Mattheisen
  36. Maciej Trzaskowski
  37. Enda M. Byrne
  38. Abdel Abdellaoui
  39. Mark J. Adams
  40. Esben Agerbo
  41. Tracy M. Air
  42. Till F. M. Andlauer
  43. Silviu-Alin Bacanu
  44. Marie Bækvad-Hansen
  45. Aartjan T. F. Beekman
  46. Tim B. Bigdeli
  47. Douglas H. R. Blackwood
  48. Julien Bryois
  49. Henriette N. Buttenschøn
  50. Jonas Bybjerg-Grauholm
  51. Na Cai
  52. Enrique Castelao
  53. Jane Hvarregaard Christensen
  54. Toni-Kim Clarke
  55. Jonathan R. I. Coleman
  56. Lucía Colodro-Conde
  57. Baptiste Couvy-Duchesne
  58. Nick Craddock
  59. Gregory E. Crawford
  60. Gail Davies
  61. Ian J. Deary
  62. Franziska Degenhardt
  63. Eske M. Derks
  64. Nese Direk
  65. Conor V. Dolan
  66. Erin C. Dunn
  67. Thalia C. Eley
  68. Valentina Escott-Price
  69. Farnush Farhadi Hassan Kiadeh
  70. Hilary K. Finucane
  71. Andreas J. Forstner
  72. Josef Frank
  73. Héléna A. Gaspar
  74. Michael Gill
  75. Fernando S. Goes
  76. Scott D. Gordon
  77. Jakob Grove
  78. Lynsey S. Hall
  79. Christine Søholm Hansen
  80. Thomas F. Hansen
  81. Stefan Herms
  82. Ian B. Hickie
  83. Per Hoffmann
  84. Georg Homuth
  85. Carsten Horn
  86. Jouke-Jan Hottenga
  87. David M. Hougaard
  88. Marcus Ising
  89. Rick Jansen
  90. Eric Jorgenson
  91. James A. Knowles
  92. Isaac S. Kohane
  93. Julia Kraft
  94. Warren W. Kretzschmar
  95. Jesper Krogh
  96. Zoltán Kutalik
  97. Yihan Li
  98. Penelope A. Lind
  99. Donald J. MacIntyre
  100. Dean F. MacKinnon
  101. Robert M. Maier
  102. Wolfgang Maier
  103. Jonathan Marchini
  104. Hamdi Mbarek
  105. Patrick McGrath
  106. Peter McGuffin
  107. Sarah E. Medland
  108. Divya Mehta
  109. Christel M. Middeldorp
  110. Evelin Mihailov
  111. Yuri Milaneschi
  112. Lili Milani
  113. Francis M. Mondimore
  114. Grant W. Montgomery
  115. Sara Mostafavi
  116. Niamh Mullins
  117. Matthias Nauck
  118. Bernard Ng
  119. Michel G. Nivard
  120. Dale R. Nyholt
  121. Paul F. O’Reilly
  122. Hogni Oskarsson
  123. Michael J. Owen
  124. Jodie N. Painter
  125. Carsten Bøcker Pedersen
  126. Marianne Giørtz Pedersen
  127. Roseann E. Peterson
  128. Erik Pettersson
  129. Wouter J. Peyrot
  130. Giorgio Pistis
  131. Danielle Posthuma
  132. Jorge A. Quiroz
  133. Per Qvist
  134. John P. Rice
  135. Brien P. Riley
  136. Margarita Rivera
  137. Saira Saeed Mirza
  138. Robert Schoevers
  139. Eva C. Schulte
  140. Ling Shen
  141. Jianxin Shi
  142. Stanley I. Shyn
  143. Engilbert Sigurdsson
  144. Grant C. B. Sinnamon
  145. Johannes H. Smit
  146. Daniel J. Smith
  147. Hreinn Stefansson
  148. Stacy Steinberg
  149. Fabian Streit
  150. Jana Strohmaier
  151. Katherine E. Tansey
  152. Henning Teismann
  153. Alexander Teumer
  154. Wesley Thompson
  155. Pippa A. Thomson
  156. Thorgeir E. Thorgeirsson
  157. Matthew Traylor
  158. Jens Treutlein
  159. Vassily Trubetskoy
  160. André G. Uitterlinden
  161. Daniel Umbricht
  162. Sandra Van der Auwera
  163. Albert M. van Hemert
  164. Alexander Viktorin
  165. Peter M. Visscher
  166. Yunpeng Wang
  167. Bradley T. Webb
  168. Shantel Marie Weinsheimer
  169. Jürgen Wellmann
  170. Gonneke Willemsen
  171. Stephanie H. Witt
  172. Yang Wu
  173. Hualin S. Xi
  174. Jian Yang
  175. Futao Zhang
  176. Volker Arolt
  177. Bernhard T. Baune
  178. Klaus Berger
  179. Dorret I. Boomsma
  180. Sven Cichon
  181. Udo Dannlowski
  182. E. J. C. de Geus
  183. J. Raymond DePaulo
  184. Enrico Domenici
  185. Katharina Domschke
  186. Tõnu Esko
  187. Hans J. Grabe
  188. Steven P. Hamilton
  189. Caroline Hayward
  190. Andrew C. Heath
  191. Kenneth S. Kendler
  192. Stefan Kloiber
  193. Glyn Lewis
  194. Qingqin S. Li
  195. Susanne Lucae
  196. Pamela A. F. Madden
  197. Patrik K. Magnusson
  198. Nicholas G. Martin
  199. Andrew M. McIntosh
  200. Andres Metspalu
  201. Ole Mors
  202. Preben Bo Mortensen
  203. Bertram Müller-Myhsok
  204. Merete Nordentoft
  205. Markus M. Nöthen
  206. Michael C. O’Donovan
  207. Sara A. Paciga
  208. Nancy L. Pedersen
  209. Brenda W. J. H. Penninx
  210. Roy H. Perlis
  211. David J. Porteous
  212. James B. Potash
  213. Martin Preisig
  214. Marcella Rietschel
  215. Catherine Schaefer
  216. Thomas G. Schulze
  217. Jordan W. Smoller
  218. Kari Stefansson
  219. Henning Tiemeier
  220. Rudolf Uher
  221. Henry Völzke
  222. Myrna M. Weissman
  223. Thomas Werge
  224. Cathryn M. Lewis
  225. Douglas F. Levinson
  226. Gerome Breen
  227. Anders D. Børglum
  228. Patrick F. Sullivan
  229. Katri Räikkönen
  230. Elisabeth B. Binder

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

  1. PublishedNature Communications10.1038/s41467-019-10461-0
  2. 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}
}
.bib file