Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Science. 2018 Dec 14;362(6420):eaat7615. doi: 10.1126/science.aat7615.

Abstract

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.

Publication types

  • Dataset
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / embryology*
  • Brain / growth & development
  • Epigenesis, Genetic
  • Epigenomics
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Humans
  • Mental Disorders / genetics*
  • Nervous System Diseases / genetics*
  • Neurogenesis / genetics*
  • Single-Cell Analysis
  • Transcriptome