Fu-Ying Tian1, Todd M Everson1, Barry Lester2, Tracy Punshon3, Brian P Jackson4, Ke Hao5, Corina Lesseur6, Jia Chen6, Margaret R Karagas7, Carmen J Marsit8. 1. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 2. Brown Center for the Study of Children at Risk, Women and Infants Hospital, Warren Alpert School of Medicine of Brown University, Providence, RI, USA. 3. Department of Biological Sciences, Dartmouth College, Hanover, NH, USA. 4. Department of Earth Sciences, Dartmouth College, Hanover, NH, USA. 5. Department of Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. Department 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, USA. 8. Department 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. Electronic address: carmen.j.marsit@emory.edu.
Abstract
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.
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.
Authors: Tracy Punshon; Zhigang Li; Carmen J Marsit; Brian P Jackson; Emily R Baker; Margaret R Karagas Journal: Environ Sci Technol Date: 2016-01-15 Impact factor: 9.028
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Authors: Lyndsey E Shorey-Kendrick; Cindy T McEvoy; Shannon M O'Sullivan; Kristin Milner; Brittany Vuylsteke; Robert S Tepper; David M Haas; Byung Park; Lina Gao; Annette Vu; Cynthia D Morris; Eliot R Spindel Journal: Clin Epigenetics Date: 2021-09-19 Impact factor: 6.551