| Literature DB >> 27040690 |
Bonnie R Joubert1, Janine F Felix2, Paul Yousefi3, Kelly M Bakulski4, Allan C Just5, Carrie Breton6, Sarah E Reese1, Christina A Markunas7, Rebecca C Richmond8, Cheng-Jian Xu9, Leanne K Küpers10, Sam S Oh11, Cathrine Hoyo12, Olena Gruzieva13, Cilla Söderhäll14, Lucas A Salas15, Nour Baïz16, Hongmei Zhang17, Johanna Lepeule18, Carlos Ruiz15, Symen Ligthart19, Tianyuan Wang1, Jack A Taylor1, Liesbeth Duijts20, Gemma C Sharp8, Soesma A Jankipersadsing21, Roy M Nilsen22, Ahmad Vaez23, M Daniele Fallin4, Donglei Hu11, Augusto A Litonjua24, Bernard F Fuemmeler25, Karen Huen3, Juha Kere14, Inger Kull13, Monica Cheng Munthe-Kaas26, Ulrike Gehring27, Mariona Bustamante28, Marie José Saurel-Coubizolles29, Bilal M Quraishi17, Jie Ren6, Jörg Tost30, Juan R Gonzalez15, Marjolein J Peters31, Siri E Håberg32, Zongli Xu1, Joyce B van Meurs31, Tom R Gaunt8, Marjan Kerkhof33, Eva Corpeleijn10, Andrew P Feinberg34, Celeste Eng11, Andrea A Baccarelli35, Sara E Benjamin Neelon4, Asa Bradman3, Simon Kebede Merid13, Anna Bergström13, Zdenko Herceg36, Hector Hernandez-Vargas36, Bert Brunekreef37, Mariona Pinart38, Barbara Heude39, Susan Ewart40, Jin Yao6, Nathanaël Lemonnier41, Oscar H Franco19, Michael C Wu42, Albert Hofman43, Wendy McArdle44, Pieter Van der Vlies45, Fahimeh Falahi10, Matthew W Gillman46, Lisa F Barcellos3, Ashish Kumar47, Magnus Wickman48, Stefano Guerra49, Marie-Aline Charles39, John Holloway50, Charles Auffray41, Henning W Tiemeier51, George Davey Smith8, Dirkje Postma52, Marie-France Hivert46, Brenda Eskenazi3, Martine Vrijheid15, Hasan Arshad53, Josep M Antó38, Abbas Dehghan19, Wilfried Karmaus17, Isabella Annesi-Maesano16, Jordi Sunyer38, Akram Ghantous36, Göran Pershagen13, Nina Holland3, Susan K Murphy54, Dawn L DeMeo24, Esteban G Burchard55, Christine Ladd-Acosta4, Harold Snieder10, Wenche Nystad32, Gerard H Koppelman56, Caroline L Relton8, Vincent W V Jaddoe2, Allen Wilcox1, Erik Melén48, Stephanie J London57.
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.Entities:
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Year: 2016 PMID： 27040690 PMCID： PMC4833289 DOI： 10.1016/j.ajhg.2016.02.019
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.043