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Lookup NU author(s): Dr Lynsey Hall
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2019, The Author(s).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.
Author(s): Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hamalainen E, Kajantie E, Laivuori H, Villa PM, Reynolds RM, Nystad W, Haberg 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, Muller 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, Baekvad-Hansen M, Beekman ATF, Bigdeli TB, Blackwood DHR, Bryois J, Buttenschon 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, Muller-Myhsok B, Nordentoft M, Nothen 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, Volzke H, Weissman MM, Werge T, Lewis CM, Levinson DF, Breen G, Borglum AD, Sullivan PF, Raikkonen K, Binder EB
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2019
Volume: 10
Issue: 1
Print publication date: 01/12/2019
Online publication date: 11/06/2019
Acceptance date: 10/05/2019
Date deposited: 26/06/2019
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41467-019-10461-0
DOI: 10.1038/s41467-019-10461-0
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