A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood.
Autism spectrum disorder
Chromatin
Environment
Gene expression
Meta-analysis
Microarray
Neurodevelopment
Perinatal
Prospective study
Umbilical cord blood
Journal
Molecular autism
ISSN: 2040-2392
Titre abrégé: Mol Autism
Pays: England
ID NLM: 101534222
Informations de publication
Date de publication:
2019
2019
Historique:
received:
25
06
2019
accepted:
08
09
2019
entrez:
2
11
2019
pubmed:
2
11
2019
medline:
18
6
2020
Statut:
epublish
Résumé
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.
Sections du résumé
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children.
Methods
Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis.
Results
While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log
Limitations
ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder.
Conclusions
This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.
Identifiants
pubmed: 31673306
doi: 10.1186/s13229-019-0287-z
pii: 287
pmc: PMC6814108
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
36Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES023780
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES029213
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES028089
Pays : United States
Organisme : NIMHD NIH HHS
ID : R01 MD013299
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES023513
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES025574
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG055406
Pays : United States
Informations de copyright
© The Author(s). 2019.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
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