TY - JOUR
T1 - Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Czamara, Darina
AU - Eraslan, Gökçen
AU - Page, Christian M.
AU - Lahti, Jari
AU - Lahti-Pulkkinen, Marius
AU - Hämäläinen, Esa
AU - Kajantie, Eero
AU - Laivuori, Hannele
AU - Villa, Pia M.
AU - Reynolds, Rebecca M.
AU - Nystad, Wenche
AU - Håberg, Siri E.
AU - London, Stephanie J.
AU - O’Donnell, Kieran J.
AU - Garg, Elika
AU - Meaney, Michael J.
AU - Entringer, Sonja
AU - Wadhwa, Pathik D.
AU - Buss, Claudia
AU - Jones, Meaghan J.
AU - Lin, David T.S.
AU - MacIsaac, Julie L.
AU - Kobor, Michael S.
AU - Koen, Nastassja
AU - Zar, Heather J.
AU - Koenen, Karestan C.
AU - Dalvie, Shareefa
AU - Stein, Dan J.
AU - Kondofersky, Ivan
AU - Müller, Nikola S.
AU - Theis, Fabian J.
AU - Wray, Naomi R.
AU - Ripke, Stephan
AU - Mattheisen, Manuel
AU - Trzaskowski, Maciej
AU - Byrne, Enda M.
AU - Abdellaoui, Abdel
AU - Adams, Mark J.
AU - Agerbo, Esben
AU - Air, Tracy M.
AU - Andlauer, Till F.M.
AU - Bacanu, Silviu Alin
AU - Bækvad-Hansen, Marie
AU - Beekman, Aartjan T.F.
AU - Bigdeli, Tim B.
AU - Blackwood, Douglas H.R.
AU - Bryois, Julien
AU - Buttenschøn, Henriette N.
AU - Bybjerg-Grauholm, Jonas
AU - Cai, Na
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85067229888&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-10461-0
DO - 10.1038/s41467-019-10461-0
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C2 - 31186427
AN - SCOPUS:85067229888
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2548
ER -