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Integrative functional genomic analysis of human brain development and neuropsychiatric risks.

  • Author(s): Li, Mingfeng
  • Santpere, Gabriel
  • Imamura Kawasawa, Yuka
  • Evgrafov, Oleg V
  • Gulden, Forrest O
  • Pochareddy, Sirisha
  • Sunkin, Susan M
  • Li, Zhen
  • Shin, Yurae
  • Zhu, Ying
  • Sousa, André MM
  • Werling, Donna M
  • Kitchen, Robert R
  • Kang, Hyo Jung
  • Pletikos, Mihovil
  • Choi, Jinmyung
  • Muchnik, Sydney
  • Xu, Xuming
  • Wang, Daifeng
  • Lorente-Galdos, Belen
  • Liu, Shuang
  • Giusti-Rodríguez, Paola
  • Won, Hyejung
  • de Leeuw, Christiaan A
  • Pardiñas, Antonio F
  • BrainSpan Consortium
  • PsychENCODE Consortium
  • PsychENCODE Developmental Subgroup
  • Hu, Ming
  • Jin, Fulai
  • Li, Yun
  • Owen, Michael J
  • O'Donovan, Michael C
  • Walters, James TR
  • Posthuma, Danielle
  • Reimers, Mark A
  • Levitt, Pat
  • Weinberger, Daniel R
  • Hyde, Thomas M
  • Kleinman, Joel E
  • Geschwind, Daniel H
  • Hawrylycz, Michael J
  • State, Matthew W
  • Sanders, Stephan J
  • Sullivan, Patrick F
  • Gerstein, Mark B
  • Lein, Ed S
  • Knowles, James A
  • Sestan, Nenad
  • et al.
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.

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