@misc{10481/57518,
year = {2019},
url = {http://hdl.handle.net/10481/57518},
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.},
organization = {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).},
publisher = {Springer Nature},
title = {Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns},
doi = {10.1038/s41467-019-10461-0},
author = {Czamara, Darina and Rivera Sánchez, Margarita},
}