Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Mingfeng Li, Gabriel Santpere, Yuka Imamura Kawasawa, Oleg V. Evgrafov, Forrest O. Gulden, Sirisha Pochareddy, Susan M. Sunkin, Zhen Li, Yurae Shin, Ying Zhu, André M.M. Sousa, Donna M. Werling, Robert R. Kitchen, Hyo Jung Kang, Mihovil Pletikos, Jinmyung Choi, Sydney Muchnik, Xuming Xu, Daifeng Wang, Belen Lorente-GaldosShuang Liu, Paola Giusti-Rodríguez, Hyejung Won, Christiaan A. De Leeuw, Antonio F. Pardiñas, Ming Hu, Fulai Jin, Yun Li, Michael J. Owen, Michael C. O'Donovan, James T.R. Walters, Danielle Posthuma, Pat Levitt, Daniel R. Weinberger, Thomas M. Hyde, Joel E. Kleinman, Daniel H. Geschwind, Michael J. Hawrylycz, Matthew W. State, Stephan J. Sanders, Patrick F. Sullivan, Mark B. Gerstein, Ed S. Lein, James A. Knowles, Nenad Sestan*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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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
Article number1264
Pages (from-to)1-15
Number of pages15
JournalScience
Volume362
Issue number6420
DOIs
Publication statusPublished - 14 Dec 2018

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