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
Year: 2019
Type: review
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: < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. 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.
Source: Molecular Autism
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,060
Funders: National Institutes of Health, National Center For Environmental Assessment, National Institute on Aging, NIH Office of the Director, National Institute of Environmental Health Sciences, National Institute of Child Health and Human Development, National Institute on Minority Health and Health Disparities, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLES, Folic Acid Prevention Pathways for ASD in High Risk Families, G3213621815, MIND Institute Intellectual and Developmental Disabilities Research Center, Autism Risk, Prenatal Environmental Exposures, and Pathophysiologic Markers, G5011760066, Racial inequalities in health throughout adulthood: The cumulative impact of neighborhood chemical and non-chemical stressors on epigenomic pathways, Prospective Evaluation of Air Pollution, Cognition, and Autism from Birth Onward, The UC Davis Center for Children's Enviromental Health and Disease Prevention, Revisiting ReCHARGE: ECHO Follow up on Middle Childhood and Adolescence, Environment, The Perinatal Epigenome, and Risk for Autism and Related Disorders, Prenatal exposure to metals and risk for Autism Spectrum Disorder in MARBLES and EARLI, Characterizing disparities in late-onset Alzheimer's disease risk through polygenic risk and epidemiologic factors in the Health and Retirement Survey, Early Autism Risk Longitudinal Investigation (EARLI) Network, Building Interdisciplinary Research Careers in Women's Health at UC Davis, Environmental Influence on Infant Microbiome Development and ASD Symptoms, PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES), G9000335535, UC Davis Environmental Health Sciences Core Center, Revisiting ReCHARGE: ECHO Follow up on Middle Childhood and Adolescence
OpenAlex ID: W2982175009