Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
Authors: Czamara Darina , Eraslan Gökçen , Page Christian M. , Lahti Jari , Lahti-Pulkkinen Marius , Hämäläinen Esa , Kajantie Eero , Laivuori Hannele , Villa Pia M. , Reynolds Rebecca M. , Nystad Wenche , Håberg 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 , Müller Nikola S. , Theis Fabian J. ,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 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 , Bækvad-Hansen Marie , Beekman Aartjan T. F. , Bigdeli Tim B. , Blackwood Douglas H. R. , Bryois Julien , Buttenschøn Henriette N. , Bybjerg-Grauholm Jonas , Cai Na , Castelao Enrique , Christensen Jane Hvarregaard , Clarke Toni-Kim , Coleman Jonathan R. I. , Colodro-Conde Lucía , 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 Héléna A. , Gill Michael , Goes Fernando S. , Gordon Scott D. , Grove Jakob , Hall Lynsey S. , Hansen Christine Søholm , 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 Zoltán , 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 Bøcker , Pedersen Marianne Giørtz , 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 André 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 Jürgen , 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 Tõnu , 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 , Müller-Myhsok Bertram , Nordentoft Merete , Nöthen 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 , Völzke Henry , Weissman Myrna M. , Werge Thomas , Lewis Cathryn M. , Levinson Douglas F. , Breen Gerome , Børglum Anders D. , Sullivan Patrick F. , Räikkönen Katri , Binder Elisabeth B. 
Published: June 2019

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.