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

Czamara, Darina; Sigurdsson, Engilbert; Stefansson, Kari

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dc.contributor	Háskóli Íslands
dc.contributor	University of Iceland
dc.contributor.author	Czamara, Darina
dc.contributor.author	Sigurdsson, Engilbert
dc.contributor.author	orcid.org/0000-0003-1676-864X Stefansson, Kari
dc.date.accessioned	2020-03-20T15:06:26Z
dc.date.available	2020-03-20T15:06:26Z
dc.date.issued	2019-06-11
dc.identifier.citation	Czamara, D., Eraslan, G., Page, C.M. et al. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nature Communications 10, 2548 (2019). https://doi.org/10.1038/s41467-019-10461-0
dc.identifier.issn	2041-1723
dc.identifier.uri	https://hdl.handle.net/20.500.11815/1633
dc.description	Publisher's version (útgefin grein)
dc.description.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.
dc.description.sponsorship	We want to thank Susanne Sauer and Maik Ködel for their technical assistance and Jessica Keverne for language editing. We thank all mothers who took part in the on-going PREDO study. We are grateful to all the families in Norway who participate in the on-going MoBa cohort study. We thank the Drakenstein Child Health Study staff, and the clinical and administrative staff of the Western Cape Government Department of Health at Paarl Hospital and at the clinics for support of the Study. We also thank our collaborators and students. Finally, we thank all mothers and children enroled in the Drakenstein Child Health Study. We thank the research participants and employees of 23andMe, Inc. for their contribution to this study. This work was supported by the Academy of Finland (E.K., H.L., K.R., and J.L.); University of Helsinki Research Funds (J.L., M.L.P., and H.L.), British Heart Foundation (RMR); Tommy’s (RMR); European Commission (EK, KR, Horizon 2020 Award SC1–2016-RTD-733280 RECAP); NorFace DIAL (E.K., KR PremLife); Foundation for Pediatric Research (E.K.); Juho Vainio Foundation (E.K.); Novo Nordisk Foundation (E.K.); Signe and Ane Gyllenberg Foundation (E.K., K.R.); Sigrid Jusélius Foundation (E.K.); Finnish Medical Foundation (H.L.); Jane and Aatos Erkko Foundation (H.L.); Päivikki and Sakari Sohlberg Foundation (H.L., P.M.V.); the Clinical Graduate school in Pediatrics and Obstetrics/Gynaecology in University of Helsinki (P.M.V.). The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537–06A1). For this work, MoBa 1 and 2 were supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-49019) and the Norwegian Research Council/BIOBANK (grant no 221097). This work was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The Drakenstein Child Health Study is supported by the Bill and Melinda Gates Foundation (OPP 1017641); with additional support for this work from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NICHD) under Award Number R21HD085849; and the Fogarty International Center (FIC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support for H.J.Z., D.J.S. and N.K., and for research reported in this publication was by the South African Medical Research Council (SAMRC); N.K. receives support from the SAMRC under a Self-Initiated Research Grant. The views and opinions expressed are those of the authors and do not necessarily represent the official views of the SAMRC. This work was also funded by the German Federal Ministry of Education and Research through the Research Consortium Integrated Network IntegraMent (grant 01ZX1314H) under the auspices of the e:Med Programme (NSM). The UCI cohort was supported by a European Research Area Network (ERA Net) Neuron grant (01EW1407A, CB) and National Institutes of Health grant (R01 HD-060628, CB) as well as NIH grant R01 MH-105538 (PDW). This work was also funded by the Canadian Institute for Advanced Research, Child and Brain Development Program, Toronto, ON, Canada (KJOD).
dc.format.extent	2548
dc.language.iso	en
dc.publisher	Springer Science and Business Media LLC
dc.relation	info:eu-repo/grantAgreement/EC/H2020/733280
dc.relation.ispartofseries	Nature Communications;10(1)
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	Biomarkers
dc.subject	DNA methylation
dc.subject	Epigenomics
dc.subject	Erfðagreining
dc.subject	Genamengi
dc.subject	DNA-rannsóknir
dc.subject	Nýburar
dc.title	Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
dc.type	info:eu-repo/semantics/article
dcterms.license	Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.description.version	Peer Reviewed
dc.identifier.journal	Nature Communications
dc.identifier.doi	10.1038/s41467-019-10461-0
dc.relation.url	https://www.nature.com/articles/s41467-019-10461-0#citeas
dc.contributor.department	Læknadeild (HÍ)
dc.contributor.department	Faculty of Medicine (UI)
dc.contributor.school	Heilbrigðisvísindasvið (HÍ)
dc.contributor.school	School of Health Sciences (UI)