Journal Article

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

Domschke, Katharina, Stein, Dan J, Kobor, Michael S, Weinsheimer, Shantel Marie, Strohmaier, Jana, Mors, Ole, Thorgeirsson, Thorgeir E, Bybjerg-Grauholm, Jonas, Peyrot, Wouter J, Mihailov, Evelin, Thomson, Pippa A, Hansen, Thomas F, O'Reilly, Paul F, Dalvie, Shareefa, Baekvad-Hansen, Marie, Herms, Stefan, Milaneschi, Yuri, Wray, Naomi R, Mattheisen, Manuel, Sullivan, Patrick F, Degenhardt, Franziska, Hamalainen, Esa, Crawford, Gregory E, Maier, Robert M, Esko, Tonu, Horn, Carsten, Escott-Price, Valentina, Mueller-Myhsok, Bertram, Hickie, Ian B, Krogh, Jesper, Haberg, Siri E, Maier, Wolfgang, Kutalik, Zoltan, Paciga, Sara A, Kendler, Kenneth S, Deary, Ian J, Lind, Penelope A, Schaefer, Catherine, Lahti-Pulkkinen, Marius, Tiemeier, Henning, Ising, Marcus, Mehta, Divya, Stefansson, Hreinn, Werge, Thomas, Zhang, Futao, Medland, Sarah E, Quiroz, Jorge A, Hansen, Christine Soholm, Shi, Jianxin, Abdellaoui, Abdel, Borglum, Anders D, Mbarek, Hamdi, Berger, Klaus, Mueller, Nikola S, Consortium, Psychiat Genomics, Heath, Andrew C, Webb, Bradley T, Madden, Pamela AF, Bryois, Julien, Lahti, Jari, Visscher, Peter M, K

2019

Overview

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. Environmental influences during prenatal development may have implications for health and disease later in life. Here, Czamara et al. assess DNA methylation in cord blood from new-born under various models including environmental and genetic effects individually and their additive or interaction effects.

• Publisher: Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 1300 Biochemistry / 1600 Chemistry / 2.1 Biological and endogenous factors / 3100 Physics and Astronomy / 45/43 / 631/208/176/1988 / 631/208/177 / 692/53 / [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology / Aetiology / biomarkers / Biomedicine / BIRTH / Blood / Childhood Maltreatment / Cohort Studies / Cohort Studies; DNA; DNA Methylation; Epigenesis, Genetic; Female; Fetal Blood; Genotype; Humans; Infant, Newborn; Male; Pregnancy; Risk Factors; Gene-Environment Interaction / Cord blood / Cord blood DNA methylation / Deoxyribonucleic acid / DNA / DNA - blood / DNA methylation / DNA Methylation - genetics / EMC MM-01-39-09-A / EMC NIHES-01-64-01 / EMC ONWAR-01-58-02 / Environmental and genetic influences / Environmental factors / Epigenesis / Epigenesis, Genetic / epigenomics / Female / Fetal Blood / Gene-Environment Interaction / Genetic / Genetic analysis / Genetic diversity / Genetic effects / Genetic variance / Genetics / Genetics and Molecular Biology / Genetics, developmental biology, physiology / Genome-Wide / GENOTYPE / Genotypes / Health risks / Human Genome / Human health and pathology / Humanities and Social Sciences / Humans / In-Utero / Infant / Infant, Newborn / Life Sciences / Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium / Male / MATERNAL SMOKING / multidisciplinary / Neonates / Netherlands Twin Register (NTR) / Newborn / Norwegian Mother / Pediatric / Pregnancy / PRENATAL STRESS / Prevention / Q / RISK / Risk Factors / Science / Science (multidisciplinary)