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

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

Am J Hum Genet 2016 Apr 31;98(4):680-96. Epub 2016 Mar 31.

National Institute of Environmental Health Sciences, NIH, U.S. Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Electronic address:

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.

Download full-text PDF

http://dx.doi.org/10.1016/j.ajhg.2016.02.019DOI Listing
April 2016

Publication Analysis

Top Keywords

maternal smoking
smoking pregnancy
dna methylation
methylation newborns
differentially methylated
cell type
relation maternal
false discovery
significance false
statistical significance
smoking genome-wide
type adjustment
genome-wide statistical
discovery rate
studies cell
2017 genes

Similar Publications