Maternal Blood Metal Concentrations and Whole Blood DNA Methylation During Pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)

Details

• Personal Author:
  Aung MT ; Bakulski KM ; Croen LA ; Dou JF ; Fallin MD ; Feinberg JI ; Hertz-Picciotto I ; Ladd-Acosta C ; Loch-Caruso R ; Meeker JD ; Mukherjee B ; Newschaffer CJ ; Volk HE
• Description:
  The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate q-value <0.1), near the genes CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead-associated sites were enriched (FDR q-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR q-value <0.1), one of which was near the gene ARID2. Manganese-associated sites were enriched for cellular metabolism pathways (FDR q-value<0.1). Effect estimates for DNA methylation sites associated (p < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways. [Description provided by NIOSH]
• Subjects:
  Cohort Studies Epidemiology Genetics Metals Occupational Health Safety
• Keywords:
  ASDs Author Keywords: DNA Methylation Autism Spectrum Disorders Cell Type Reference Cellular Heterogeneity Cohort Studies DNA Damage Epigenetics Longitudinal Study Saliva Trace Metals

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• ISSN:
  1559-2294
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Maryland ; Michigan ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  253-268
• Volume:
  17
• Issue:
  3
• NIOSHTIC Number:
  nn:20070654
• Citation:
  Epigenetics 2022 Mar; 17(3):253-268
• Contact Point Address:
  Kelly M. Bakulski, Department of Epidemiology, University of Michigan M5511 SPH II 1415 Washington Heights, Ann Arbor, MI 48109-2029
• Email:
  bakulski@umich.edu
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Lead (CAS RN 7439-92-1) ; Manganese (CAS RN 7439-96-5)
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Epigenetics
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8990d0d787ba3268934809fd6705258118fe86e62165f1da75a32186e14979d2167be8297a7fc56da308d43c0df7282383eeb747f339b38fd35ccd0ffed91650
• Download URL:
  https://stacks.cdc.gov/view/cdc/208832/cdc_208832_DS1.pdf
• File Type:
  [PDF - 1.86 MB ]