DNA methylation in newborns and maternal smoking in pregnancy : genome-wide consortium meta-analysis

Joubert, Bonnie R. and Felix, Janine F. and Yousefi, Paul and Bakulski, Kelly M. and Just, Allan C. and Breton, Carrie and Reese, Sarah E. and Markunas, Christina A. and Richmond, Rebecca C. and Xu, Cheng-Jian and Küpers, Leanne K. and Oh, Sam S. and Hoyo, Cathrine and Gruzieva, Olena and Söderhäll, Cilla and Salas, Lucas A. and Baïz, Nour and Zhang, Hongmei and Lepeule, Johanna and Ruiz, Carlos and Ligthart, Symen and Wang, Tianyuan and Taylor, Jack A. and Duijts, Liesbeth and Sharp, Gemma C. and Jankipersadsing, Soesma A. and Nilsen, Roy M. and Vaez, Ahmad and Fallin, M. Daniele and Hu, Donglei and Litonjua, Augusto A. and Fuemmeler, Bernard F. and Huen, Karen and Kere, Juha and Kull, Inger and Munthe-Kaas, Monica Cheng and Gehring, Ulrike and Bustamante, Mariona and Saurel-Coubizolles, Marie José and Quraishi, Bilal M. and Ren, Jie and Tost, Jörg and Gonzalez, Juan R. and Peters, Marjolein J. and Håberg, Siri E. and Xu, Zongli and van Meurs, Joyce B. and Gaunt, Tom R. and Kerkhof, Marjan and Corpeleijn, Eva and Feinberg, Andrew P. and Eng, Celeste and Baccarelli, Andrea A. and Benjamin Neelon, Sara E. and Bradman, Asa and Merid, Simon Kebede and Bergström, Anna and Herceg, Zdenko and Hernandez-Vargas, Hector and Brunekreef, Bert and Pinart, Mariona and Heude, Barbara and Ewart, Susan and Yao, Jin and Lemonnier, Nathanaël and Franco, Oscar H. and Wu, Michael C. and Hofman, Albert and McArdle, Wendy and Van der Vlies, Pieter and Falahi, Fahimeh and Gillman, Matthew W. and Barcellos, Lisa F. and Kumar, Ashish and Wickman, Magnus and Guerra, Stefano and Charles, Marie-Aline and Holloway, John and Auffray, Charles and Tiemeier, Henning W. and Smith, George Davey and Postma, Dirkje and Hivert, Marie-France and Eskenazi, Brenda and Vrijheid, Martine and Arshad, Hasan and Antó, Josep M. and Dehghan, Abbas and Karmaus, Wilfried and Annesi-Maesano, Isabella and Sunyer, Jordi and Ghantous, Akram and Pershagen, Göran and Holland, Nina and Murphy, Susan K. and DeMeo, Dawn L. and Burchard, Esteban G. and Ladd-Acosta, Christine and Snieder, Harold and Nystad, Wenche and Koppelman, Gerard H. and Relton, Caroline L. and Jaddoe, Vincent W. V. and Wilcox, Allen and Melén, Erik and London, Stephanie J.. (2016) DNA methylation in newborns and maternal smoking in pregnancy : genome-wide consortium meta-analysis. American journal of human genetics, 98 (4). pp. 680-696.

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Official URL: http://edoc.unibas.ch/42437/

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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.

Faculties and Departments:	09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) 09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Exposome Science (Probst-Hensch) 03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Exposome Science (Probst-Hensch)
UniBasel Contributors:	Kumar, Ashish
Item Type:	Article, refereed
Article Subtype:	Research Article
Publisher:	Univ. of Chicago Press
ISSN:	0002-9297
Note:	Publication type according to Uni Basel Research Database: Journal article
Identification Number:	doi: 10.1016/j.ajhg.2016.02.019 pmid: 27040690
Last Modified:	30 Jun 2016 11:03
Deposited On:	26 May 2016 08:42

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