DNA Methylation at Birth Potentially Mediates the Association Between Prenatal Lead (Pb) Exposure and Infant Neurodevelopmental Outcomes

Details

• Personal Author:
  Aung MT ; Bakulski KM ; Dolinoy DC ; Goodrich JM ; Hu H ; Jones TR ; Marcela E ; Perng W ; Peterson KE ; Rygiel CA ; Schnaas L ; Solano-González M ; Tellez-Rojo MM
• Description:
  Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, P < 0.1 was considered significant. DNAm at a locus in CCSER1 (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), P = 0.06] and emotional regulation [3.62 (-0.05, 8.69), P = 0.05]. Cg18515027 (GCNT1) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), P = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), P = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), P = 0.09]. The indirect effect was significant for cg19703494 (TRAPPC6A) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), P = 0.05]. There was also an indirect effect of cg23280166 (VPS11) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), P = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Epidemiology Genetics Lead Occupational Health Pregnancy Safety
• Keywords:
  Author Keywords: Epigenetics Developmental Exposure Developmental Programming DNA Damage Environmental Exposure Longitudinal Study Neurodevelopment Pb Prenatal Exposure
• ISSN:
  2058-5888
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Colorado ; Michigan ; OSHA Region 5 ; OSHA Region 8 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-12
• Volume:
  7
• Issue:
  1
• NIOSHTIC Number:
  nn:20070652
• Citation:
  Environ Epigenet 2021 Jun; 7(1):1-12
• Contact Point Address:
  Jaclyn M Goodrich, Environmental Health Sciences, University of Michigan, School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA
• Email:
  gaydojac@umich.edu
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  2021
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Environmental Epigenetics
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:baef49e0b30eb78ab01483bda14e94043254048d3f94778b583183f68c9881a0e4c64e34e07f3de3ba86d0e0da088e2ce3b201c7d7c57291680c0321675f30de
• Download URL:
  https://stacks.cdc.gov/view/cdc/208830/cdc_208830_DS1.pdf
• File Type:
  [PDF - 502.62 KB ]