Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth
Gestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbi...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
SAGE Publishing
2020-07-01
|
Series: | Epigenetics Insights |
Online Access: | https://doi.org/10.1177/2516865720938669 |
id |
doaj-80ff76e4f7564117a70da56e2437cad8 |
---|---|
record_format |
Article |
spelling |
doaj-80ff76e4f7564117a70da56e2437cad82020-11-25T03:10:13ZengSAGE PublishingEpigenetics Insights2516-86572020-07-011310.1177/2516865720938669Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at BirthChristine A Rygiel0Dana C Dolinoy1Wei Perng2Tamara R Jones3Maritsa Solano4Howard Hu5Martha M Téllez-Rojo6Karen E Peterson7Jaclyn M Goodrich8Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USADepartment of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USADepartment of Epidemiology, University of Colorado School of Public Health, Denver, CO, USADepartment of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USANational Institute of Public Health, Cuernavaca, MexicoDepartment of Environmental and Occupational Health Sciences, University of Washington School of Public Health, Seattle, WA, USANational Institute of Public Health, Cuernavaca, MexicoDepartment of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USADepartment of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USAGestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbilical cord blood (UCB) leukocytes. Eighty-nine mother-child dyads from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) longitudinal birth cohorts with available UCB samples were selected for DNA methylation analysis via the Infinium Methylation EPIC BeadChip, which quantifies methylation at >850 000 CpG sites. Maternal blood lead levels (BLLs) during each trimester (T1: 6.56 ± 5.35 µg/dL; T2: 5.93 ± 5.00 µg/dL; T3: 6.09 ± 4.51 µg/dL), bone Pb (patella: 11.8 ± 9.25 µg/g; tibia: 11.8 ± 6.73 µg/g), a measure of cumulative Pb exposure, and UCB Pb (4.86 ± 3.74 µg/dL) were measured. After quality control screening, data from 786 024 CpG sites were used to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by Pb biomarkers using separate linear regression models, controlling for sex and estimated UCB cell-type proportions. We identified 3 DMPs associated with maternal T1 BLL, 2 with T3 BLL, and 2 with tibia bone Pb. We identified one DMR within PDGFRL associated with T1 BLL, one located at chr6:30095136-30095295 with T3 BLL, and one within TRHR with tibia bone Pb (adjusted P -value < .05). Pathway analysis identified 15 overrepresented gene pathways for differential methylation that overlapped among all 3 trimesters with the largest overlap between T1 and T2 (adjusted P -value < .05). Pathways of interest include nodal signaling pathway and neurological system processes. These data provide evidence for differential methylation by prenatal Pb exposure that may be trimester-specific.https://doi.org/10.1177/2516865720938669 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine A Rygiel Dana C Dolinoy Wei Perng Tamara R Jones Maritsa Solano Howard Hu Martha M Téllez-Rojo Karen E Peterson Jaclyn M Goodrich |
spellingShingle |
Christine A Rygiel Dana C Dolinoy Wei Perng Tamara R Jones Maritsa Solano Howard Hu Martha M Téllez-Rojo Karen E Peterson Jaclyn M Goodrich Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth Epigenetics Insights |
author_facet |
Christine A Rygiel Dana C Dolinoy Wei Perng Tamara R Jones Maritsa Solano Howard Hu Martha M Téllez-Rojo Karen E Peterson Jaclyn M Goodrich |
author_sort |
Christine A Rygiel |
title |
Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth |
title_short |
Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth |
title_full |
Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth |
title_fullStr |
Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth |
title_full_unstemmed |
Trimester-Specific Associations of Prenatal Lead Exposure With Infant Cord Blood DNA Methylation at Birth |
title_sort |
trimester-specific associations of prenatal lead exposure with infant cord blood dna methylation at birth |
publisher |
SAGE Publishing |
series |
Epigenetics Insights |
issn |
2516-8657 |
publishDate |
2020-07-01 |
description |
Gestational exposure to lead (Pb) adversely impacts offspring health through multiple mechanisms, one of which is the alteration of the epigenome including DNA methylation. This study aims to identify differentially methylated CpG sites associated with trimester-specific maternal Pb exposure in umbilical cord blood (UCB) leukocytes. Eighty-nine mother-child dyads from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) longitudinal birth cohorts with available UCB samples were selected for DNA methylation analysis via the Infinium Methylation EPIC BeadChip, which quantifies methylation at >850 000 CpG sites. Maternal blood lead levels (BLLs) during each trimester (T1: 6.56 ± 5.35 µg/dL; T2: 5.93 ± 5.00 µg/dL; T3: 6.09 ± 4.51 µg/dL), bone Pb (patella: 11.8 ± 9.25 µg/g; tibia: 11.8 ± 6.73 µg/g), a measure of cumulative Pb exposure, and UCB Pb (4.86 ± 3.74 µg/dL) were measured. After quality control screening, data from 786 024 CpG sites were used to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) by Pb biomarkers using separate linear regression models, controlling for sex and estimated UCB cell-type proportions. We identified 3 DMPs associated with maternal T1 BLL, 2 with T3 BLL, and 2 with tibia bone Pb. We identified one DMR within PDGFRL associated with T1 BLL, one located at chr6:30095136-30095295 with T3 BLL, and one within TRHR with tibia bone Pb (adjusted P -value < .05). Pathway analysis identified 15 overrepresented gene pathways for differential methylation that overlapped among all 3 trimesters with the largest overlap between T1 and T2 (adjusted P -value < .05). Pathways of interest include nodal signaling pathway and neurological system processes. These data provide evidence for differential methylation by prenatal Pb exposure that may be trimester-specific. |
url |
https://doi.org/10.1177/2516865720938669 |
work_keys_str_mv |
AT christinearygiel trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT danacdolinoy trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT weiperng trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT tamararjones trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT maritsasolano trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT howardhu trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT marthamtellezrojo trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT karenepeterson trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth AT jaclynmgoodrich trimesterspecificassociationsofprenatalleadexposurewithinfantcordblooddnamethylationatbirth |
_version_ |
1724659909706907648 |