Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes

View ORCID ProfileCharles E. Mordaunt, Julia M. Jianu, View ORCID ProfileBen Laufer, View ORCID ProfileYihui Zhu, View ORCID ProfileKeith W. Dunaway, View ORCID ProfileKelly M. Bakulski, View ORCID ProfileJason I. Feinberg, View ORCID ProfileHeather E. Volk, View ORCID ProfileKristen Lyall, Lisa A. Croen, View ORCID ProfileCraig J. Newschaffer, View ORCID ProfileSally Ozonoff, View ORCID ProfileIrva Hertz-Picciotto, View ORCID ProfileM. Daniele Fallin, View ORCID ProfileRebecca J. Schmidt, View ORCID ProfileJanine M. LaSalle
doi: https://doi.org/10.1101/850529
Charles E. Mordaunt
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Charles E. Mordaunt
Julia M. Jianu
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ben Laufer
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ben Laufer
Yihui Zhu
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yihui Zhu
Keith W. Dunaway
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Keith W. Dunaway
Kelly M. Bakulski
2Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kelly M. Bakulski
Jason I. Feinberg
3Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jason I. Feinberg
Heather E. Volk
3Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heather E. Volk
Kristen Lyall
4A. J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kristen Lyall
Lisa A. Croen
5Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Craig J. Newschaffer
6Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, University Park, PA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Craig J. Newschaffer
Sally Ozonoff
7Psychiatry and Behavioral Sciences and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sally Ozonoff
Irva Hertz-Picciotto
8Department of Public Health Sciences and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Irva Hertz-Picciotto
M. Daniele Fallin
3Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for M. Daniele Fallin
Rebecca J. Schmidt
8Department of Public Health Sciences and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rebecca J. Schmidt
Janine M. LaSalle
1Department of Medical Microbiology and Immunology, Genome Center, and MIND Institute, University of California, Davis, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Janine M. LaSalle
  • For correspondence: jmlasalle@ucdavis.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Data/Code
  • Preview PDF
Loading

Abstract

Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. Since the neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development, we performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth.

Results We identified differentially-methylated regions (DMRs) stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development.

Conclusions At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD, and provides novel insights for early diagnosis and therapy.

Footnotes

  • cemordaunt{at}ucdavis.edu, jmjianu{at}ucdavis.edu, blaufer{at}ucdavis.edu, yhzhu{at}ucdavis.edu, kwdunaway{at}ucdavis.edu, bakulski{at}umich.edu, jfeinbe2{at}jhu.edu, hvolk1{at}jhu.edu, kld98{at}drexel.edu, lisa.a.croen{at}kp.org, cjn5389{at}psu.edu, sozonoff{at}ucdavis.edu, ihp{at}ucdavis.edu, dfallin{at}jhu.edu, rjschmidt{at}ucdavis.edu, jmlasalle{at}ucdavis.edu

  • https://github.com/cemordaunt/AutismCordBloodMethylation

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted November 21, 2019.
Download PDF

Supplementary Material

Data/Code
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
Charles E. Mordaunt, Julia M. Jianu, Ben Laufer, Yihui Zhu, Keith W. Dunaway, Kelly M. Bakulski, Jason I. Feinberg, Heather E. Volk, Kristen Lyall, Lisa A. Croen, Craig J. Newschaffer, Sally Ozonoff, Irva Hertz-Picciotto, M. Daniele Fallin, Rebecca J. Schmidt, Janine M. LaSalle
bioRxiv 850529; doi: https://doi.org/10.1101/850529
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
Charles E. Mordaunt, Julia M. Jianu, Ben Laufer, Yihui Zhu, Keith W. Dunaway, Kelly M. Bakulski, Jason I. Feinberg, Heather E. Volk, Kristen Lyall, Lisa A. Croen, Craig J. Newschaffer, Sally Ozonoff, Irva Hertz-Picciotto, M. Daniele Fallin, Rebecca J. Schmidt, Janine M. LaSalle
bioRxiv 850529; doi: https://doi.org/10.1101/850529

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2647)
  • Biochemistry (5271)
  • Bioengineering (3682)
  • Bioinformatics (15799)
  • Biophysics (7261)
  • Cancer Biology (5629)
  • Cell Biology (8102)
  • Clinical Trials (138)
  • Developmental Biology (4769)
  • Ecology (7524)
  • Epidemiology (2059)
  • Evolutionary Biology (10588)
  • Genetics (7734)
  • Genomics (10138)
  • Immunology (5199)
  • Microbiology (13921)
  • Molecular Biology (5392)
  • Neuroscience (30805)
  • Paleontology (215)
  • Pathology (879)
  • Pharmacology and Toxicology (1525)
  • Physiology (2256)
  • Plant Biology (5026)
  • Scientific Communication and Education (1042)
  • Synthetic Biology (1389)
  • Systems Biology (4150)
  • Zoology (812)