Autism-Associated DNA Methylation at Birth from Multiple Tissues Is Enriched for Autism Genes in the Early Autism Risk Longitudinal Investigation

Details

• Personal Author:
  Aung MT ; Bakulski KM ; Croen LA ; Dou JF ; Fallin MD ; Feinberg AP ; Feinberg JI ; Hertz-Picciotto I ; Ladd-Acosta C ; Landa R ; Levy SE ; Newschaffer CJ ; Volk HE
• Description:
  Background: Pregnancy measures of DNA methylation, an epigenetic mark, may be associated with autism spectrum disorder (ASD) development in children. Few ASD studies have considered prospective designs with DNA methylation measured in multiple tissues and tested overlap with ASD genetic risk loci. Objectives: To estimate associations between DNA methylation in maternal blood, cord blood, and placenta and later diagnosis of ASD, and to evaluate enrichment of ASD-associated DNA methylation for known ASD-associated genes. Methods: In the Early Autism Risk Longitudinal Investigation (EARLI), an ASD-enriched risk birth cohort, genome-scale maternal blood (early n = 140 and late n = 75 pregnancy), infant cord blood (n = 133), and placenta (maternal n = 106 and fetal n = 107 compartments) DNA methylation was assessed on the Illumina 450k HumanMethylation array and compared to ASD diagnosis at 36 months of age. Differences in site-specific and global methylation were tested with ASD, as well as enrichment of single site associations for ASD risk genes (n = 881) from the Simons Foundation Autism Research Initiative (SFARI) database. Results: No individual DNA methylation site was associated with ASD at genome-wide significance, however, individual DNA methylation sites nominally associated with ASD (P < 0.05) in each tissue were highly enriched for SFARI genes (cord blood P = 7.9 × 10-29, maternal blood early pregnancy P = 6.1 × 10-27, maternal blood late pregnancy P = 2.8 × 10-16, maternal placenta P = 5.6 × 10-15, fetal placenta P = 1.3 × 10-20). DNA methylation sites nominally associated with ASD across all five tissues overlapped at 144 (29.5%) SFARI genes. Conclusion: DNA methylation sites nominally associated with later ASD diagnosis in multiple tissues were enriched for ASD risk genes. Our multi-tissue study demonstrates the utility of examining DNA methylation prior to ASD diagnosis. [Description provided by NIOSH]
• Subjects:
  Biomarkers Epidemiology Genetics Occupational Health Safety
• Keywords:
  ASDs Author Keywords: Autism Spectrum Disorder Autism Spectrum Disorders Biomarker Cord Blood DNA Methylation Longitudinal Study Molecular Signaling
• ISSN:
  1662-5099
• 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
• Volume:
  14
• NIOSHTIC Number:
  nn:20070644
• Citation:
  Front Mol Neurosci 2021 Nov; 14:775390
• Contact Point Address:
  Margaret D. Fallin, Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States
• Email:
  dfallin@jhu.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Frontiers in Molecular Neuroscience
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7fd11749cfdf3ab80ce99609dee160ad0557e6721688d2a265e5001114b460445f38d8969d2c19df97bfe035417db7062ac13e15c84474eb8decf15bae5d33b
• Download URL:
  https://stacks.cdc.gov/view/cdc/208823/cdc_208823_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]