ArticleInternational journal of epidemiology2015
DNA methylation mediates the effect of maternal smoking during pregnancy on birthweight of the offspring.
Article in International journal of epidemiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 8 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 8 syntheses or guidelines pooled it.
- DNA methylation in peripheral tissues and left-handedness.Scientific reports · 2022Pooled it
- Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.Molecular psychiatry · 2022Pooled it
- Pooled it
- Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.Nature communications · 2019Pooled it
- Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.EBioMedicine · 2018Pooled it
- Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review.Annals of global health · 2018Pooled it
- Maternal alcohol consumption and offspring DNA methylation: findings from six general population-based birth cohorts.Epigenomics · 2018Pooled it
- DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.American journal of human genetics · 2016Pooled it
- An epigenome-wide study of a needs-based family intervention for offspring of trauma-exposed mothers in Kosovo.Brain and behavior · 2024Trial
- Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age.Clinical epigenetics · 2024Trial
- Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy.American journal of respiratory and critical care medicine · 2017Trial
- Maternal BMI associations with cord blood DNA methylation and mid-childhood adiposity.Clinical epigenetics · 2026Observational
- Blood and adipose tissue DNA methylation in adults born preterm with a very low birth weight - a sibling comparison study.Epigenomics · 2026Article
- Epigenetic Alterations Induced by Smoking and Their Intersection with Artificial Intelligence: A Narrative Review.International journal of environmental research and public health · 2025Review
- Immediate and durable effects of maternal tobacco consumption on placental DNA methylation: a replication and discovery study.Environmental epigenetics · 2025Article
- Association of exposure to second-hand smoke during childhood with blood DNA methylation.Environment international · 2025Article
- Second phase Chiba study of mother and child health (C-MACH): Japanese birth cohort study with multiomics analyses.BMJ open · 2024Article
- Integrative analysis of genetics, epigenetics and RNA expression data reveal three susceptibility loci for smoking behavior in Chinese Han population.Molecular psychiatry · 2024Article
- Developmental origins of psycho-cardiometabolic multimorbidity in adolescence and their underlying pathways through methylation markers: a two-cohort study.European child & adolescent psychiatry · 2024Article
- Article
61 more citing papers are in PubMed but not listed here.
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17 authors.
Funding
Abstract
backgroundWe examined whether the effect of maternal smoking during pregnancy on birthweight of the offspring was mediated by smoking-induced changes to DNA methylation in cord blood.
methodsFirst, we used cord blood of 129 Dutch children exposed to maternal smoking vs 126 unexposed to maternal and paternal smoking (53% male) participating in the GECKO Drenthe birth cohort. DNA methylation was measured using the Illumina HumanMethylation450 Beadchip. We performed an epigenome-wide association study for the association between maternal smoking and methylation followed by a mediation analysis of the top signals [false-discovery rate (FDR) < 0.05]. We adjusted both analyses for maternal age, education, pre-pregnancy BMI, offspring's sex, gestational age and white blood cell composition. Secondly, in 175 exposed and 1248 unexposed newborns from two independent birth cohorts, we replicated and meta-analysed results of eight cytosine-phosphate-guanine (CpG) sites in the GFI1 gene, which showed the most robust mediation. Finally, we performed functional network and enrichment analysis.
resultsWe found 35 differentially methylated CpGs (FDR < 0.05) in newborns exposed vs unexposed to smoking, of which 23 survived Bonferroni correction (P < 1 × 10(-7)). These 23 CpGs mapped to eight genes: AHRR, GFI1, MYO1G, CYP1A1, NEUROG1, CNTNAP2, FRMD4A and LRP5. We observed partial confirmation as three of the eight CpGs in GFI1 replicated. These CpGs partly mediated the effect of maternal smoking on birthweight (Sobel P < 0.05) in meta-analysis of GECKO and the two replication cohorts. Differential methylation of these three GFI1 CpGs explained 12-19% of the 202 g lower birthweight in smoking mothers. Functional enrichment analysis pointed towards activation of cell-mediated immunity.
conclusionsMaternal smoking during pregnancy was associated with cord blood methylation differences. We observed a potentially mediating role of methylation in the association between maternal smoking during pregnancy and birthweight of the offspring. Functional network analysis suggested a role in activating the immune system.
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