Integrative functional genomic analysis of human brain development and neuropsychiatric risks

BrainSpan Consortium, PsychENCODE Consortium, PsychENCODE Developmental Subgroup

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1264
JournalScience
Volume362
Issue number6420
DOIs
StatePublished - Dec 14 2018

ASJC Scopus subject areas

  • General

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    BrainSpan Consortium, PsychENCODE Consortium, & PsychENCODE Developmental Subgroup (2018). Integrative functional genomic analysis of human brain development and neuropsychiatric risks. Science, 362(6420), [1264]. https://doi.org/10.1126/science.aat7615