1. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis
- Author
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Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Neelon, Sara E Benjamin, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, and Nystad, Wenche
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Health Sciences ,Genetics ,Human Genome ,Prevention ,Tobacco Smoke and Health ,Tobacco ,Perinatal Period - Conditions Originating in Perinatal Period ,Pediatric ,Clinical Research ,2.1 Biological and endogenous factors ,Reproductive health and childbirth ,Respiratory ,Good Health and Well Being ,Asthma ,Child ,Child ,Preschool ,Chromosome Mapping ,Cleft Lip ,Cleft Palate ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Genetic Association Studies ,Humans ,Infant ,Infant ,Newborn ,Pregnancy ,Smoking ,White People ,Medical and Health Sciences ,Genetics & Heredity ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - 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.
- Published
- 2016