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, Bios Consortium, 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, Jack A Taylor, Janine F Felix, Siri E Håberg, Mariona Bustamante, Stephanie J London
{"title":"Prenatal Smoking Exposures and Epigenome-wide Methylation in Newborn Blood.","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, Bios Consortium, 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, Jack A Taylor, Janine F Felix, Siri E Håberg, Mariona Bustamante, Stephanie J London","doi":"10.1289/EHP16303","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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, paternal quitting before pregnancy).</p><p><strong>Methods: </strong>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 on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array.</p><p><strong>Results: </strong>Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] <0.05) at 8,862 CpGs on the 450K (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 (<i>MED13L</i>) was associated with 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.</p><p><strong>Conclusions: </strong>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. https://doi.org/10.1289/EHP16303.</p>","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":" ","pages":""},"PeriodicalIF":10.1000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Health Perspectives","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1289/EHP16303","RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
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, 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 on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K 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 450K (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 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. https://doi.org/10.1289/EHP16303.
期刊介绍：
Environmental Health Perspectives (EHP) is a monthly peer-reviewed journal supported by the National Institute of Environmental Health Sciences, part of the National Institutes of Health under the U.S. Department of Health and Human Services. Its mission is to facilitate discussions on the connections between the environment and human health by publishing top-notch research and news. EHP ranks third in Public, Environmental, and Occupational Health, fourth in Toxicology, and fifth in Environmental Sciences.
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