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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Li, M; Santpere, G; Imamura Kawasawa, Y; Evgrafov, OV; Gulden, FO; Pochareddy, S; Sunkin, SM; Li, Z; Shin, Y; Zhu, Y; Sousa, AMM; Werling, DM; Kitchen, RR; Kang, HJ; Pletikos, M; Choi, J; Muchnik, S; Xu, X; Wang, D; Lorente-Galdos, B; Liu, S; Giusti-Rodríguez, P; Won, H; de Leeuw, CA; Pardiñas, AF; BrainSpan Consortium, ; PsychENCODE Consortium, ; PsychENCODE Developmental Subgroup, ; Hu, M; Jin, F; Li, Y; Owen, MJ; O'Donovan, MC; Walters, JTR; Posthuma, D; Reimers, MA; Levitt, P; Weinberger, DR; Hyde, TM; Kleinman, JE; Geschwind, DH; Hawrylycz, MJ; State, MW; Sanders, SJ; Sullivan, PF; Gerstein, MB; Lein, ES; Knowles, JA; Sestan, N

Published Date

  • December 2018

Published In

Volume / Issue

  • 362 / 6420

PubMed ID

  • 30545854

Pubmed Central ID

  • 30545854

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.aat7615

Language

  • eng