%0 Journal Article
%T DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis
%A Abbas Dehghan
%A Ahmad Vaez
%A Akram Ghantous
%A Albert Hofman
%A Allan£¿C. Just
%A Allen Wilcox
%A Andrea£¿A. Baccarelli
%A Andrew£¿P. Feinberg
%A Anna Bergstr£¿m
%A Asa Bradman
%A Ashish Kumar
%A Augusto£¿A. Litonjua
%A Barbara Heude
%A Bernard£¿F. Fuemmeler
%A Bert Brunekreef
%A Bilal£¿M. Quraishi
%A Bonnie£¿R. Joubert
%A Brenda Eskenazi
%A Carlos Ruiz
%A Caroline£¿L. Relton
%A Carrie Breton
%A Cathrine Hoyo
%A Celeste Eng
%A Charles Auffray
%A Cheng-Jian Xu
%A Christina£¿A. Markunas
%A Christine Ladd-Acosta
%A Cilla S£¿derh£¿ll
%A Dawn£¿L. DeMeo
%A Dirkje Postma
%A Donglei Hu
%A Erik Mel¨¦n
%A Esteban£¿G. Burchard
%A Eva Corpeleijn
%A Fahimeh Falahi
%A Gemma£¿C. Sharp
%A George£¿Davey Smith
%A Gerard£¿H. Koppelman
%A G£¿ran Pershagen
%A Harold Snieder
%A Hasan Arshad
%A Hector Hernandez-Vargas
%A Henning£¿W. Tiemeier
%A Hongmei Zhang
%A Inger Kull
%A Isabella Annesi-Maesano
%A Jack£¿A. Taylor
%A Janine£¿F. Felix
%A Jie Ren
%A Jin Yao
%A Johanna Lepeule
%A John Holloway
%A Jordi Sunyer
%A Josep£¿M. Ant¨®
%A Joyce£¿B. van£¿Meurs
%A Juan£¿R. Gonzalez
%A Juha Kere
%A J£¿rg Tost
%A Karen Huen
%A Kelly£¿M. Bakulski
%A Leanne£¿K. K¨¹pers
%A Liesbeth Duijts
%A Lisa£¿F. Barcellos
%A Lucas£¿A. Salas
%A M.£¿Daniele Fallin
%A Magnus Wickman
%A Marie-Aline Charles
%A Marie-France Hivert
%A Marie£¿Jos¨¦ Saurel-Coubizolles
%A Mariona Bustamante
%A Mariona Pinart
%A Marjan Kerkhof
%A Marjolein£¿J. Peters
%A Martine Vrijheid
%A Matthew£¿W. Gillman
%A Michael£¿C. Wu
%A Monica£¿Cheng Munthe-Kaas
%A Nathana£¿l Lemonnier
%A Nina Holland
%A Nour Ba£¿z
%A Olena Gruzieva
%A Oscar£¿H. Franco
%A Paul Yousefi
%A Pieter Van£¿der£¿Vlies
%A Rebecca£¿C. Richmond
%A Roy£¿M. Nilsen
%A Sam£¿S. Oh
%A Sarah E. Reese
%A Sara£¿E. Benjamin£¿Neelon
%A Simon£¿Kebede Merid
%A Siri£¿E. H£¿berg
%A Soesma£¿A. Jankipersadsing
%J Archive of "American Journal of Human Genetics".
%D 2016
%R 10.1016/j.ajhg.2016.02.019
%X 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 ¡Á 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
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833289/