Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.
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ABSTRACT:
SUBMITTER: Sikdar S
PROVIDER: S-EPMC6836223 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Comparison of smoking-related DNA methylation between newborns from prenatal exposure and adults from personal smoking.
Sikdar Sinjini S Joehanes Roby R Joubert Bonnie R BR Xu Cheng-Jian CJ Vives-Usano Marta M Rezwan Faisal I FI Felix Janine F JF Ward James M JM Guan Weihua W Richmond Rebecca C RC Brody Jennifer A JA Küpers Leanne K LK Baïz Nour N Håberg Siri E SE Smith Jennifer A JA Reese Sarah E SE Aslibekyan Stella S Hoyo Cathrine C Dhingra Radhika R Markunas Christina A CA Xu Tao T Reynolds Lindsay M LM Just Allan C AC Mandaviya Pooja R PR Ghantous Akram A Bennett Brian D BD Wang Tianyuan T Consortium The Bios TB Bakulski Kelly M KM Melen Erik E Zhao Shanshan S Jin Jianping J Herceg Zdenko Z Meurs Joyce van JV Taylor Jack A JA Baccarelli Andrea A AA Murphy Susan K SK Liu Yongmei Y Munthe-Kaas Monica Cheng MC Deary Ian J IJ Nystad Wenche W Waldenberger Melanie M Annesi-Maesano Isabella I Conneely Karen K Jaddoe Vincent Wv VW Arnett Donna D Snieder Harold H Kardia Sharon Lr SL Relton Caroline L CL Ong Ken K KK Ewart Susan S Moreno-Macias Hortensia H Romieu Isabelle I Sotoodehnia Nona N Fornage Myriam M Motsinger-Reif Alison A Koppelman Gerard H GH Bustamante Mariona M Levy Daniel D London Stephanie J SJ
Epigenomics 20190919 13
<b>Aim:</b> Cigarette smoking influences DNA methylation genome wide, in newborns from pregnancy exposure and in adults from personal smoking. Whether a unique methylation signature exists for <i>in utero</i> exposure in newborns is unknown. <b>Materials & methods:</b> We separately meta-analyzed newborn blood DNA methylation (assessed using Illumina450k Beadchip), in relation to sustained maternal smoking during pregnancy (9 cohorts, 5648 newborns, 897 exposed) and adult blood methylation and p ...[more]
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Project description:BackgroundMaternal smoking during pregnancy is associated with significant infant morbidity and mortality, and may influence later disease risk. One mechanism by which smoking (and other environmental factors) might have long-lasting effects is through epigenetic modifications such as DNA methylation.ObjectivesWe conducted an epigenome-wide association study (EWAS) investigating alterations in DNA methylation in infants exposed in utero to maternal tobacco smoke, using the Norway Facial Clefts Study.MethodsThe Illumina HumanMethylation450 BeadChip was used to assess DNA methylation in whole blood from 889 infants shortly after delivery. Of 889 mothers, 287 reported smoking-twice as many smokers as in any previous EWAS of maternal smoking. CpG sites related to maternal smoking during the first trimester were identified using robust linear regression.ResultsWe identified 185 CpGs with altered methylation in infants of smokers at genome-wide significance (q-value < 0.05; mean Δβ = ± 2%). These correspond to 110 gene regions, of which 7 have been previously reported and 10 are newly confirmed using publicly available results. Among these 10, the most noteworthy are FRMD4A, ATP9A, GALNT2, and MEG3, implicated in processes related to nicotine dependence, smoking cessation, and placental and embryonic development.ConclusionsOur study identified 10 genes with newly established links to maternal smoking. Further, we note differences between smoking-related methylation changes in newborns and adults, suggesting possible distinct effects of direct versus indirect tobacco smoke exposure as well as potential differences due to age. Further work would be needed to determine whether these small changes in DNA methylation are biologically or clinically relevant. The methylation changes identified in newborns may mediate the association between in utero maternal smoking exposure and later health outcomes.
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Project description:Tobacco smoking is a preventable environmental factor that contributes to a wide spectrum of age-related health outcomes; however, its association with the development of frailty is not yet well established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with a quantitative frailty index (FI) in 2 independent subsets of older adults (age 50-75) recruited in Saarland, Germany in 2000 - 2002 (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina HumanMethylation450 BeadChip and calculated the FI according to the method of Mitnitski and Rockwood. Mixed linear regression models were implemented to assess the associations between smoking indicators and the FI. After controlling for potential covariates, current smoking, cumulative smoking exposure (pack-years), and time after smoking cessation (years) were significantly associated with the FI (P-value < 0.05). In the discovery panel, 17 out of 151 previously identified smoking-related CpG sites were associated with the FI after correction for multiple testing (FDR < 0.05). Nine of them survived in the validation phase and were designated as frailty-associated loci. A smoking index (SI) based on the 9 loci manifested a monotonic association with the FI. In conclusion, this study suggested that epigenetic alterations could play a role in smoking-associated development of frailty. The identified CpG sites have the potential to be prognostic biomarkers of frailty and frailty-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.
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