Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts
Background/Aim: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA me...
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Elsevier
2020-04-01
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Series: | Environment International |
Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412019320136 |
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author | Fu-Ying Tian Todd M. Everson Barry Lester Tracy Punshon Brian P. Jackson Ke Hao Corina Lesseur Jia Chen Margaret R. Karagas Carmen J. Marsit |
author_facet | Fu-Ying Tian Todd M. Everson Barry Lester Tracy Punshon Brian P. Jackson Ke Hao Corina Lesseur Jia Chen Margaret R. Karagas Carmen J. Marsit |
author_sort | Fu-Ying Tian |
collection | DOAJ |
description | Background/Aim: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns’ neurobehavior. Methods: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. Results: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (β-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). Conclusions: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association. Keywords: Selenium, DNA methylation, Placenta, Neurobehavior, NNNS, Muscle tone |
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id | doaj.art-ed6c039ee26d4affb9b4d2fe47d33396 |
institution | Directory Open Access Journal |
issn | 0160-4120 |
language | English |
last_indexed | 2024-04-12T01:08:18Z |
publishDate | 2020-04-01 |
publisher | Elsevier |
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series | Environment International |
spelling | doaj.art-ed6c039ee26d4affb9b4d2fe47d333962022-12-22T03:54:12ZengElsevierEnvironment International0160-41202020-04-01137Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohortsFu-Ying Tian0Todd M. Everson1Barry Lester2Tracy Punshon3Brian P. Jackson4Ke Hao5Corina Lesseur6Jia Chen7Margaret R. Karagas8Carmen J. Marsit9Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USADepartment of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USABrown Center for the Study of Children at Risk, Women and Infants Hospital, Warren Alpert School of Medicine of Brown University, Providence, RI, USADepartment of Biological Sciences, Dartmouth College, Hanover, NH, USADepartment of Earth Sciences, Dartmouth College, Hanover, NH, USADepartment of Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA; Children’s Environmental Health and Disease Prevention Research Center at Dartmouth, Dartmouth College, Lebanon, NH, USADepartment of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA; Children’s Environmental Health and Disease Prevention Research Center at Dartmouth, Dartmouth College, Lebanon, NH, USA; Corresponding author at: Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.Background/Aim: Selenium (Se) levels in pregnancy have been linked to neurobehavioral development of the offspring. DNA methylation is a potential mechanism underlying the impacts of environmental exposures on fetal development; however, very few studies have been done elucidating the role of DNA methylation linking prenatal Se and child neurobehavior. We aimed to investigate the associations between placental Se concentration and epigenome-wide DNA methylation in two U.S. cohorts, and to assess the association between Se-related DNA methylation modifications and newborns’ neurobehavior. Methods: We measured placental Se concentrations in 343 newborns enrolled in the New Hampshire Birth Cohort Study and in 141 newborns in the Rhode Island Child Health Study. Genome-wide placental DNA methylation was measured by HumanMethylation450 BeadChip, and newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales (NNNS). We meta-analyzed the associations between placental Se concentration and DNA methylation in each cohort, adjusting for covariates. We also fit multiple linear regression and ordinal logistic regression for methylation and newborn NNNS summary scores. Results: We identified five Se-related differentially methylated CpG sites. Among them was cg09674502 (GFI1), where selenium concentration was positively associated with methylation (β-coefficient = 1.11, FDR-adjusted p-value = 0.045), and where we observed that a one percent methylation level increase was associated with a 15% reduced odds of higher muscle tone in the arms, legs and trunk of newborns, (OR [95% Confidence Interval, CI] = 0.85 [0.77, 0.95]). We also observed for each interquartile range (IQR) increase in selenium concentration in the placenta, there was 1.76 times greater odds of higher hypotonicity (OR [95% CI] = 1.76 [1.12, 2.82]). Conclusions: Placental selenium concentration was inversely associated with muscle tone of newborns, and hypermethylation of GFI1 could be a potential mechanism underlying this association. Keywords: Selenium, DNA methylation, Placenta, Neurobehavior, NNNS, Muscle tonehttp://www.sciencedirect.com/science/article/pii/S0160412019320136 |
spellingShingle | Fu-Ying Tian Todd M. Everson Barry Lester Tracy Punshon Brian P. Jackson Ke Hao Corina Lesseur Jia Chen Margaret R. Karagas Carmen J. Marsit Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts Environment International |
title | Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts |
title_full | Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts |
title_fullStr | Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts |
title_full_unstemmed | Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts |
title_short | Selenium-associated DNA methylation modifications in placenta and neurobehavioral development of newborns: An epigenome-wide study of two U.S. birth cohorts |
title_sort | selenium associated dna methylation modifications in placenta and neurobehavioral development of newborns an epigenome wide study of two u s birth cohorts |
url | http://www.sciencedirect.com/science/article/pii/S0160412019320136 |
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