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450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy

Type
Journal article
Peer reviewed
publishedVersion
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Date
2012-10
Author
Joubert, Bonnie R.
Håberg, Siri Eldevik
Nilsen, Roy Miodini
Wang, Xuting
Vollset, Stein Emil
Murphy, Susan K
Huang, Zhiqing
Hoyo, Cathrine
Midttun, Øivind
Cupul-Uicab, Lea A
Ueland, Per Magne
Wu, Michael C
Nystad, Wenche
Bell, Douglas A
Peddada, Shyamal D
London, Stephanie J
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Abstract
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.
URI
http://hdl.handle.net/1956/12165
DOI
10.1289/ehp.1205412
Citation
Environmental Health Perspectives 2012, 120(10):1425-1431
Publisher
The National Institute of Environmental Health Sciences
Collections
  • Department of Global Public Health and Primary Care 942
Copyright law does not apply to Environmental Health Perspectives, which falls within the public domain.

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