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DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

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dc.contributor.author Joubert, Bonnie R.
dc.contributor.author Salas Díaz, Lucas Andrés, 1980-
dc.contributor.author Ruiz, Carlos
dc.contributor.author Bustamante Pineda, Mariona
dc.contributor.author Gonzalez, Juan Ramon
dc.contributor.author Pinart, Mariona
dc.contributor.author Guerra, Stefano
dc.contributor.author Vrijheid, Martine
dc.contributor.author Antó i Boqué, Josep Maria
dc.contributor.author Sunyer Deu, Jordi
dc.contributor.author London, Stephanie J.
dc.date.accessioned 2017-02-08T08:17:35Z
dc.date.available 2017-02-08T08:17:35Z
dc.date.issued 2016
dc.identifier.citation Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C [et. al.]. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis. American Journal of Human Genetics. 2016;98(4):680-96. DOI: 10.1016/j.ajhg.2016.02.019
dc.identifier.issn 0002-9297
dc.identifier.uri http://hdl.handle.net/10230/28075
dc.description.abstract Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10−16). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.
dc.description.sponsorship The BAMSE cohort was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Freemason Child House Foundation in Stockholm, MeDALL (Mechanisms of the Development of ALLergy), a collaborative project conducted within the European Union (grant agreement No. 261357), Centre for Allergy Research, Stockholm County Council (ALF), Swedish foundation for strategic research (SSF, RBc08-0027, EpiGene project), the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet, The Swedish Research Council Formas and the Swedish Environment Protection Agency.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof American Journal of Human Genetics. 2016;98(4):680-96
dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.ajhg.2016.02.019 that appeared in the journal American Journal of Human Genetics.It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: http://www.elsevier.com/about/open-access/open-access-policies/oa-license-policy/elsevier-user-license
dc.title DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.ajhg.2016.02.019
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261357
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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