450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy

By Bonnie R. Joubert, S. Håberg, R. M. Nilsen, Xuting Wang, S. Vollset, S. Murphy, Zhiqing Huang, C. Hoyo, Ø. Midttun, Lea A. Cupul‐Uicab and 6 more. Environmental Health Perspectives, 2012

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Background: Epigenetic modifications, such as DNA methylation, due to in utero exposures may play a critical role in early programming for childhood and adult illness. Maternal smoking is a major risk factor for multiple adverse health outcomes in children, but the underlying mechanisms are unclear. Objective: We investigated epigenome-wide methylation in cord blood of newborns in relation to maternal smoking during pregnancy. Methods: We examined maternal plasma cotinine (an objective biomarker of smoking) measured during pregnancy in relation to DNA methylation at 473,844 CpG sites (CpGs) in 1,062 newborn cord blood samples from the Norwegian Mother and Child Cohort Study (MoBa) using the Infinium HumanMethylation450 BeadChip (450K). Results: We found differential DNA methylation at epigenome-wide statistical significance (p-value < 1.06 × 10–7) for 26 CpGs mapped to 10 genes. We replicated findings for CpGs in AHRR, CYP1A1, and GFI1 at strict Bonferroni-corrected statistical significance in a U.S. birth cohort. AHRR and CYP1A1 play a key role in the aryl hydrocarbon receptor signaling pathway, which mediates the detoxification of the components of tobacco smoke. GFI1 is involved in diverse developmental processes but has not previously been implicated in responses to tobacco smoke. Conclusions: We identified a set of genes with methylation changes present at birth in children whose mothers smoked during pregnancy. This is the first study of differential methylation across the genome in relation to maternal smoking during pregnancy using the 450K platform. Our findings implicate epigenetic mechanisms in the pathogenesis of the adverse health outcomes associated with this important in utero exposure.

Subfields: Health, Toxicology and Mutagenesis, Molecular Biology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/3ac0d4a6a9895448dfa52fec40276bb3472f1445

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In Health, Toxicology and Mutagenesis

Annette Peters

In Molecular Biology

Citations in the corpus

Functional normalization of 450k methylation array data improves replication in large cancer studies (2014, methodology): “We chose to remove these loci post-normalization as done previously [16,58], reasoning that while these probes may lead to spurious associations, we believe they are still subject to technical variation and should therefore contain information useful for normalization.”
Polycyclic aromatic hydrocarbons: from metabolism to lung cancer. (2015, background): “Recent studies also suggest an important role for CYPs in the detoxification of PAHs (Arlt et al., 2012; Joubert et al., 2012).”
ENmix: a novel background correction method for Illumina HumanMethylation450 BeadChip (2015, methodology): “Using the 26 probes previously reported by Joubert (16), we examined P-values in the Markunas raw data, and following ENmix or ENmix combined with other steps.”
DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. (2016, neutral): “64 3 10 (193)), which has been observed as differentially methylated in relation to smoking in many studies of adults and children.(7,8,10,28,35,53) Our enrichment testing of the genome-wide results is in line with previous findings showing that island shores, enhancers, and DNase I hypersensitive s”
Tobacco Smoking Leads to Extensive Genome-Wide Changes in DNA Methylation (2013, methodology): “Until now, three studies concerning tobacco smoking have been accomplished with the 450K BeadChip, one using a small number of lymphoblasts and pulmonary macrophages of current and never smokers [12], another one using cord blood samples from newborns to study the effect of maternal smoking [16], an”
DNA methylation and healthy human aging (2015, background): “…signature, cigarette smoke has been linked to changes in DNA methylation at the AHRR locus both in smokers and in children of smokers (Saxonov et al., 2006; Monick et al., 2012; Joubert et al., 2012; Shenker et al., 2013; Sun et al., 2013 Elliott et al., 2014; Lee et al., 2014; Shah et al., 2014).”