Integrative functional genomic analysis of human brain development and neuropsychiatric risks.
To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
Duke Scholars
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Related Subject Headings
- Transcriptome
- Single-Cell Analysis
- Neurogenesis
- Nervous System Diseases
- Mental Disorders
- Humans
- General Science & Technology
- Gene Regulatory Networks
- Gene Expression Regulation, Developmental
- Epigenomics
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- Transcriptome
- Single-Cell Analysis
- Neurogenesis
- Nervous System Diseases
- Mental Disorders
- Humans
- General Science & Technology
- Gene Regulatory Networks
- Gene Expression Regulation, Developmental
- Epigenomics