Integrative functional genomic analysis of human brain development and neuropsychiatric risks.
Journal Article (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.
- 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
- December 14, 2018
Volume / Issue
- 362 / 6420
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States