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


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.

SUBMITTER: Joubert BR 

PROVIDER: S-EPMC4833289 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

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

American journal of human genetics 20160331 4


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  ...[more]

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