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