DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis
2016
Joubert, Bonnie R. | Felix, Janine F. | Yousefi, Paul | Bakulski, Kelly M. | Just, Allan C. | Breton, Carrie | Reese, Sarah | Markunas, Christina A. | Richmond, Rebecca C. | Xu, Cheng-Jian | Küpers, Leanne K. | Oh, Sam S. | Hoyo, Cathrine | Gruzieva, Olena | Söderhäll, Cilla | Salas, Lucas A. | Baïz, Nour | Zhang, Hongmei | Lepeule, Johanna | Ruiz, Carlos | Ligthart, Symen | Wang, Tianyuan | Taylor, Jack A. | Duijts, Liesbeth | Sharp, Gemma C. | Jankipersadsing, Soesma A. | Nilsen, Roy M. | Vaez, Ahmad | Fallin, M. Daniele | Hu, Donglei | Litonjua, Augusto A. | Fuemmeler, Bernard F. | Huen, Karen | Kere, Juha | Kull, Inger | Munthe-Kaas, Monica Cheng | Gehring, Ulrike | Bustamante, Mariona | Saurel-Coubizolles, Marie José | Quraishi, Bilal M. | Ren, Jie | Tost, Jörg | Gonzalez, Juan R. | Peters, Marjolein J. | Håberg, Siri E. | Xu, Zongli | van Meurs, Joyce B. | Gaunt, Tom R. | Kerkhof, Marjan | Corpeleijn, Eva | Feinberg, Andrew P. | Eng, Celeste | Baccarelli, Andrea A. | Benjamin Neelon, Sara E. | Bradman, Asa | Merid, Simon Kebede | Bergström, Anna | Herceg, Zdenko | Hernandez-Vargas, Hector | Brunekreef, Bert | Pinart, Mariona | Heude, Barbara | Ewart, Susan | Yao, Jin | Lemonnier, Nathanaël | Franco, Oscar H. | Wu, Michael C. | Hofman, Albert | Mcardle, Wendy | van der Vlies, Pieter | Falahi, Fahimeh | Gillman, Matthew W. | Barcellos, Lisa F. | Kumar, Ashish | Wickman, Magnus | Guerra, Stefano | Charles, Marie-Aline | Holloway, John | Auffray, Charles | Tiemeier, Henning W. | Smith, George Davey | Postma, Dirkje | Hivert, Marie-France | Eskenazi, Brenda | Vrijheid, Martine | Arshad, Hasan | Antó, Josep M. | Dehghan, Abbas | Karmaus, Wilfried | Annesi-Maesano, Isabella | Sunyer, Jordi | Ghantous, Akram | Pershagen, Göran | Holland, Nina | Murphy, Susan K. | Demeo, Dawn L. | Burchard, Esteban G. | Ladd-Acosta, Christine | Snieder, Harold | Nystad, Wenche | Koppelman, Gerard H. | Relton, Caroline L. | Jaddoe, Vincent W.V. | Wilcox, Allen | Melén, Erik | London, Stephanie J. | University of Bristol [Bristol] | University of Michigan [Ann Arbor] ; University of Michigan System | University of Southern California (USC) | National Institutes of Health [Bethesda, MD, USA] (NIH) | University of Groningen [Groningen] | North Carolina State University [Raleigh] (NC State) ; University of North Carolina System (UNC) | Department of Environmental Sciences , Vytautas Magnus University , Kaunas | Karolinska Institutet [Stockholm] | Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP) ; Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR) ; Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) | University of Memphis (U of M) | Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823) ; Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [CHU Grenoble] (CHUGA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM) | Centro Universitario de Ciencias Económico Administrativas (CUCEA) ; Universidad de Guadalajara | Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre National de Génotypage (CNG) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA) | Laboratoire Epigénétique et environnement (LEE) ; Centre National de Recherche en Génomique Humaine (CNRGH) ; Institut de Biologie François JACOB (JACOB) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Biologie François JACOB (JACOB) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) | Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC) ; Organisation Mondiale de la Santé / World Health Organization Office [Genève, Suisse] (OMS / WHO) | Equipe 6 : ORCHAD - Origines précoces de la santé du développement de l'enfant (CRESS - U1153) ; Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)) ; Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM) | European Institute for Systems Biology and Medicine (EISBM) | National Institute of Environmental Health Sciences [Durham, NC, USA] (NIEHS-NIH) ; National Institutes of Health [Bethesda, MD, USA] (NIH)
International audience
Show more [+] Less [-]English. 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.
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