Integrative functional genomic analysis of human brain development and neuropsychiatric risks

BrainSpan Consortium, PsychENCODE Consortium, PsychENCODE Developmental Subgroup

Research output: Contribution to journalArticle

54 Citations (Scopus)

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
JournalScience
Volume362
Issue number6420
DOIs
Publication statusPublished - 2018 Dec 14

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Human Development
Epigenomics
Brain
Gene Regulatory Networks
Genes

ASJC Scopus subject areas

  • General

Cite this

BrainSpan Consortium, PsychENCODE Consortium, & PsychENCODE Developmental Subgroup (2018). Integrative functional genomic analysis of human brain development and neuropsychiatric risks. Science, 362(6420), [1264]. https://doi.org/10.1126/science.aat7615

Integrative functional genomic analysis of human brain development and neuropsychiatric risks. / BrainSpan Consortium; PsychENCODE Consortium; PsychENCODE Developmental Subgroup.

In: Science, Vol. 362, No. 6420, 1264, 14.12.2018.

Research output: Contribution to journalArticle

BrainSpan Consortium, PsychENCODE Consortium & PsychENCODE Developmental Subgroup 2018, 'Integrative functional genomic analysis of human brain development and neuropsychiatric risks', Science, vol. 362, no. 6420, 1264. https://doi.org/10.1126/science.aat7615
BrainSpan Consortium, PsychENCODE Consortium, PsychENCODE Developmental Subgroup. Integrative functional genomic analysis of human brain development and neuropsychiatric risks. Science. 2018 Dec 14;362(6420). 1264. https://doi.org/10.1126/science.aat7615
BrainSpan Consortium ; PsychENCODE Consortium ; PsychENCODE Developmental Subgroup. / Integrative functional genomic analysis of human brain development and neuropsychiatric risks. In: Science. 2018 ; Vol. 362, No. 6420.
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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.",
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AU - Evgrafov, Oleg V.

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AU - Pletikos, Mihovil

AU - Choi, Jinmyung

AU - Muchnik, Sydney

AU - Xu, Xuming

AU - Wang, Daifeng

AU - Lorente-Galdos, Belen

AU - Liu, Shuang

AU - Giusti-Rodríguez, Paola

AU - Won, Hyejung

AU - De Leeuw, Christiaan A.

AU - Pardiñas, Antonio F.

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AU - Willsey, A. J.

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AU - Szafer, A.

AU - Camarena, A.

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AU - Charney, A. W.

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AU - Kozlenkov, A.

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AU - Sekijima, A.

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AU - Sboner, A.

AU - Clark, A.

AU - Jaffe, A. E.

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