Saliva Cell Type DNA Methylation Reference Panel for Epidemiological Studies in Children

Details

• Personal Author:
  Bakulski KM ; Colacino JA ; Dou J ; Faul J ; Fisher J ; Heiss JA ; Just AC ; Middleton LYM ; Mitchell C ; Nguyen VK ; Ware EB
• Description:
  Saliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7-16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 181,577 (22.8%) DNA methylation sites (t-test p < 6.28 × 10-8). Immune cell hypomethylated sites are mapped to genes enriched for immune pathways (p < 3.2 × 10-5). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10-4), a key process for hard palette formation. Saliva immune and epithelial cells have distinct DNA methylation profiles which can drive whole-saliva DNA methylation measures. A primary saliva DNA methylation reference panel, easily implemented with an R package, will allow estimates of cell proportions from whole saliva samples and improve epigenetic epidemiology studies by accounting for measurement heterogeneity by cell-type proportions. [Description provided by NIOSH]
• Subjects:
  Biomarkers Epidemiology Genetics Occupational Health Safety
• Keywords:
  Author Keywords: DNA Methylation Biological Materials Cell Type Cell Type Reference Cellular Heterogeneity Children DNA Damage Epigenetics Saliva
• ISSN:
  1559-2294
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; New York ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  161-177
• Volume:
  17
• Issue:
  2
• NIOSHTIC Number:
  nn:20070653
• Citation:
  Epigenetics 2022 Feb; 17(2):161-177
• Contact Point Address:
  Colter Mitchell, ISR, 426 Thompson St, Ann Arbor, MI, 48106
• Email:
  cmsm@umich.edu
• 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-512:276cf5138bfeb74c1f0107f091e3c5d59de8d0bccdcf4ebd97dfda34e63ca0b2e36c40dba165807296f8f81a1428844a30a0f9e4faeda85e0708450f741af7d7
• Download URL:
  https://stacks.cdc.gov/view/cdc/208831/cdc_208831_DS1.pdf
• File Type:
  [PDF - 2.46 MB ]