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

Nat Commun 2019 06 11;10(1):2548. Epub 2019 Jun 11.

Max-Planck-Institute of Psychiatry, Department of Translational Research in Psychiatry, Munich, 80804, Germany.

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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http://dx.doi.org/10.1038/s41467-019-10461-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559955PMC
June 2019
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References

(Supplied by CrossRef)

T Roseboom et al.
Early Hum. Dev. 2006

DJ Barker et al.
N. Engl. J. Med. 2005

P Hovi et al.
N. Engl. J. Med. 2007

TA Hillier et al.
Diabetes Care 2007

KN Dancause et al.
J. Obes. 2015

M Lahti et al.
J. Am. Acad. Child Adolesc. Psychiatry 2017

SL Bronson et al.
Neuropsychopharmacology 2016

CE Schwarze et al.
Psychol. Med. 2013

S Entringer et al.
Psychoneuroendocrinology 2015

M Gutierrez-Arcelus et al.
Elife 2013

BR Joubert et al.
Am. J. Hum. Genet. 2016

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