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

Autor: Charles E. Mordaunt, Bo Y. Park, Kelly M. Bakulski, Jason I. Feinberg, Lisa A. Croen, Christine Ladd-Acosta, Craig J. Newschaffer, Heather E. Volk, Sally Ozonoff, Irva Hertz-Picciotto, Janine M. LaSalle, Rebecca J. Schmidt, M. Daniele Fallin
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Autism, Vol 10, Iss 1, Pp 1-21 (2019)
Druh dokumentu: article
ISSN: 2040-2392
DOI: 10.1186/s13229-019-0287-z
Popis: Abstract 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 (log2(fold change) > 0.1, p
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