Implications of Prenatal Exposure to Hyperandrogen for Hippocampal Neurodevelopment and Autism-like Behavior in Offspring
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PROVIDER: PRJNA1033587 | ENA |
REPOSITORIES: ENA
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Project description:The prenatal period is a critical window to study factors involved in the development of autism spectrum disorder (ASD). Environmental factors, especially in utero nutrition, can interact with genetic risk for ASD, but how specific prenatal nutrients in mothers of children later diagnosed with ASD or non-typical development (Non-TD) associate with gestational gene expression events is poorly understood. Maternal blood collected prospectively during pregnancy provides a new opportunity to gain insights into nutritional effects on gene pathways and neurodevelopment. Using differential gene expression analysis, six transcripts associated with four genes (TGR-AS1, SQSTM1, HLA-C and RFESD) showed genome-wide significance (FDR q < 0.05) with child outcomes. Genes nominally differentially expressed compared to TD (p < 0.05) specifically in ASD, but not Non-TD, significantly overlapped with seven high confidence ASD genes. 218 transcripts in common to ASD and Non-TD differential expression compared to TD were significantly enriched for functions in immune response to interferon-gamma, apoptosis, and metal ion transport. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG and betaine. A module enriched in DNA methylation functions showed a protective association with folic acid/5-MeTHF concentrations and ASD risk. Independent of child outcome, maternal plasma betaine and DMG concentrations associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results support the premise that the prenatal maternal blood transcriptome is a sensitive indicator of gestational nutrition and children’s later neurodevelopmental outcomes.
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