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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.* ; Jones, M.J.* ; Lin, D.T.S.* ; MacIsaac, J.L.* ; Kobor, M.S.* ; Koen, N.* ; Zar, H.J.* ; Koenen, K.C.* ; Dalvie, S.* ; Stein, D.J.* ; Kondofersky, I. ; Müller, N.S. ; Theis, F.J. ; Räikkönen, K.* ; Binder, E.B.*

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

Nat. Commun. 10:2548 (2019)

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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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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Childhood Maltreatment; Norwegian Mother; Maternal Smoking; Prenatal Stress; Genome-wide; In-utero; Pregnancy; Risk; Birth; Genotype

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 10, Issue: 1, Article Number: 2548

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)