Loading...
Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.
Czamara, Darina; Eraslan, GƶkƧen; Page, Christian M; Lahti, Jari; Lahti-Pulkkinen, Marius; HƤmƤlƤinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M; Reynolds, Rebecca M; Nystad, Wenche; HĆ„berg, Siri E; London, Stephanie J; O'Donnell, Kieran J; Garg, Elika; Meaney, Michael J; Entringer, Sonja; Wadhwa, Pathik D; Buss, Claudia; Jones, Meaghan J; Lin, David T S; MacIsaac, Julie L; Kobor, Michael S; Koen, Nastassja; Zar, Heather J; Koenen, Karestan C; Dalvie, Shareefa; Stein, Dan J; Kondofersky, Ivan; MĆ¼ller, Nikola S; Theis, Fabian J; RƤikkƶnen, Katri; Binder, Elisabeth B
Journal Title
Nature communications
Keywords
Readers/Advisors
Journal Title
Term and Year
Publication Date
2019-06-11
Book Title
Publication Volume
10
Publication Issue
1
Publication Begin
2548
Publication End
Number of pages
Collections
Files
Loading...
s41467-019-10461-0.pdf
Adobe PDF, 1.06 MB
Research Projects
Organizational Units
Journal Issue
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 nā=ā2365). 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 (Gā+āE) 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, Gā+āE or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
Citation
Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, HƤmƤlƤinen E, Kajantie E, Laivuori H, Villa PM, Reynolds RM, Nystad W, HĆ„berg SE, London SJ, O'Donnell KJ, Garg E, Meaney MJ, Entringer S, Wadhwa PD, Buss C, Jones MJ, Lin DTS, MacIsaac JL, Kobor MS, Koen N, Zar HJ, Koenen KC, Dalvie S, Stein DJ, Kondofersky I, MĆ¼ller NS, Theis FJ; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; RƤikkƶnen K, Binder EB. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns. Nat Commun. 2019 Jun 11;10(1):2548. doi: 10.1038/s41467-019-10461-0. PMID: 31186427; PMCID: PMC6559955.