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450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy
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....
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Institute of Environmental Health Sciences
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491949/ https://www.ncbi.nlm.nih.gov/pubmed/22851337 http://dx.doi.org/10.1289/ehp.1205412 |
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author | Joubert, Bonnie R. Håberg, Siri E. Nilsen, Roy M. Wang, Xuting Vollset, Stein E. Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Midttun, Øivind Cupul-Uicab, Lea A. Ueland, Per M. Wu, Michael C. Nystad, Wenche Bell, Douglas A. Peddada, Shyamal D. London, Stephanie J. |
author_facet | Joubert, Bonnie R. Håberg, Siri E. Nilsen, Roy M. Wang, Xuting Vollset, Stein E. Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Midttun, Øivind Cupul-Uicab, Lea A. Ueland, Per M. Wu, Michael C. Nystad, Wenche Bell, Douglas A. Peddada, Shyamal D. London, Stephanie J. |
author_sort | Joubert, Bonnie R. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3491949 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | National Institute of Environmental Health Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-34919492012-11-08 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy Joubert, Bonnie R. Håberg, Siri E. Nilsen, Roy M. Wang, Xuting Vollset, Stein E. Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Midttun, Øivind Cupul-Uicab, Lea A. Ueland, Per M. Wu, Michael C. Nystad, Wenche Bell, Douglas A. Peddada, Shyamal D. London, Stephanie J. Environ Health Perspect Research 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. National Institute of Environmental Health Sciences 2012-07-31 2012-10 /pmc/articles/PMC3491949/ /pubmed/22851337 http://dx.doi.org/10.1289/ehp.1205412 Text en http://creativecommons.org/publicdomain/mark/1.0/ Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, ?Reproduced with permission from Environmental Health Perspectives?); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright. |
spellingShingle | Research Joubert, Bonnie R. Håberg, Siri E. Nilsen, Roy M. Wang, Xuting Vollset, Stein E. Murphy, Susan K. Huang, Zhiqing Hoyo, Cathrine Midttun, Øivind Cupul-Uicab, Lea A. Ueland, Per M. Wu, Michael C. Nystad, Wenche Bell, Douglas A. Peddada, Shyamal D. London, Stephanie J. 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title | 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title_full | 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title_fullStr | 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title_full_unstemmed | 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title_short | 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking during Pregnancy |
title_sort | 450k epigenome-wide scan identifies differential dna methylation in newborns related to maternal smoking during pregnancy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491949/ https://www.ncbi.nlm.nih.gov/pubmed/22851337 http://dx.doi.org/10.1289/ehp.1205412 |
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