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Publications

Journal Article Meta-Analysis Epublish

PubMed: 42428256 DOI: 10.1021/EHP.6c00142

Prenatal Smoking Exposures and Epigenome-Wide Methylation in Newborn Blood.

Environ Health Perspect 134(3):289-302

Authors: Thanh T Hoang, Marta Cosin-Tomas, Yunsung Lee, Giulietta Monasso, Zongli Xu, Sebastian Shaobo Li, Xuehuo Zeng, Anne P Starling, Brigitte Reimann, Stefan Röder, Lea Zillich, Dereje D Jima, Chris H L Thio, Giancarlo Pesce, Elin T G Kersten, Charles E Breeze, Adam B Burkholder, Mikyeong Lee, James M Ward, Rossella Alfano, Michael Deuschle, Liesbeth Duijts, Akhgar Ghassabian, Laura-Concepció Gómez Herrera, Vincent Wv Jaddoe, Alison A Motsinger-Reif, Rolv T Lie, Tim S Nawrot, Christian M Page, Tabea S Send, Gemma Sharp, Dan J Stein, Fabian Streit, Jordi Sunyer, Allen J Wilcox, Heather J Zar, Gerard H Koppelman, Isabella Annesi-Maesano, Eva Corpeleijn, Harold Snieder, Cathrine Hoyo, Anke Hüls, Lea Sirignano, Stephanie H Witt, Gunda Herberth, Michelle Plusquin, Dana Dabelea, Edwina Yeung, Joseph L Wiemels, Rebecca C Richmond … and 5 other authors

Affiliations

  • Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
  • Department of Pediatrics, Division of Hematology-Oncology, Baylor College of Medicine, Houston, Texas 77030, United States.
  • Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas 77030, United States.
  • Cancer and Hematology Center, Texas Children's Hospital, Houston, Texas 77030, United States.
  • ISGlobal, Barcelona Institute for Global Health, 08036 Barcelona, Spain.
  • Universitat Pompeu Fabra (UPF), 08005 Barcelona, Spain.
  • Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), 28029 Madrid, Spain.
  • Centre for Fertility and Health, Norwegian Institute of Public Health, 0213 Oslo, Norway.
  • The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
  • Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
  • Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, United States.
  • Center for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, California 90089, United States.
  • Glotech, Inc. Rockville, Maryland 20850, United States.
  • Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
  • Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
  • Centre for Environmental Sciences (CMK), Hasselt University, 3590 Diepenbeek, Belgium.
  • Department of Environmental Immunology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.
  • Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.
  • Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina 27695, United States.
  • Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina 27607, United States.
  • Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
  • Epidemiology of Allergic and Respiratory Diseases (EPAR) Team, Faculté de Médecine Saint-Antoine, Institute Pierre Louis d'Epidemiologie et Sante Publique (IPLESP), Sorbonne Université and INSERM UMR-S 1136, Paris, France.
  • Certara Italy, 20124 Milan, Italy.
  • University Medical Center Groningen, University of Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, 9713 GZ Groningen, The Netherlands.
  • University Medical Center Groningen, University of Groningen, Groningen Research Institute of Asthma and COPD (GRIAC), 9713 RB Groningen, The Netherlands.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
  • Office of Environmental Science Cyberinfrastructure, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
  • Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, United States.
  • Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.
  • Department of Pediatrics, Division of Respiratory Medicine and Allergology a Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
  • Department of Pediatrics, New York University Grossman School of Medicine, New York, New York 10016, United States.
  • Department of Population Health, New York University Grossman School of Medicine, New York, New York 10016, United States.
  • Universitat de Barcelona (UB), 08007 Barcelona, Spain.
  • Department of Global Public Health and Primary Care, University of Bergen, N-5020 Bergen, Norway.
  • Centre for Environmental Sciences, Hasselt University, 3500 Hasselt, Belgium.
  • Health and Environment Unit, Leuven University, 3000 Leuven Belgium.
  • Department of Physical Health and Ageing, Division of Public Health and Prevention, Norwegian Institute of Public Health, 0213 Oslo, Norway.
  • School of Psychology, University of Exeter, Exeter EX4 4QG, United Kingdom.
  • Department of Psychiatry, Neuroscience Institute, Faculty of Health Sciences, University of Cape Town, Cape Town 7701, South Africa.
  • South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Cape Town 7505, South Africa.
  • German Center for Mental Health (DZPG), partner site Mannheim-Heidelberg-Ulm, 68195 Mannheim, Germany.
  • Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68135 Mannheim, Germany.
  • IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003, Spain.
  • Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, United States.
  • Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and South African Medical Research Council (SAMRC) Unit on Child and Adolescent Health, Cape Town 7700, South Africa.
  • Institute Desbrest of Epidemiology and Public Health UMR1318, INSERM et Université de Montpellier, Montpellier 34295, France.
  • Department of Pulmonology, Allergy and Thoracic Oncology, University Hospital of Montpellier, Montpellier 34295, France.
  • Toxicology Program, North Carolina State University, Raleigh, North Carolina 27695, United States.
  • Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina 27695, United States.
  • Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, United States.
  • Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, United States.
  • Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, United States.
  • Center for Innovative Psychiatry and Psychotherapy Research (ZIPP), Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
  • Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20892, United States.
  • MRC Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, United Kingdom.
  • Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, United Kingdom.

Abstract

BACKGROUND: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, and paternal quitting before pregnancy). METHODS: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data for maternal SHS and smoking during pregnancy. Primary analyses used Illumina450 K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] < 0.05) at 8,862 CpGs on the 450 K (n = 8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (MED13L) was associated with former paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n = 3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking, and paternal smoking.

MeSH

Research Design, Genes, Pregnancy, Blood, Infant, Newborn, Tobacco Smoking, Cotinine, Epigenome, Environmental Health, Environment, Smoking