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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Science (American Association for the Advancement of Science), 2018-12, Vol.362 (6420), p.1264 [Peer Reviewed Journal]

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. ;Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works ;ISSN: 0036-8075 ;ISSN: 1095-9203 ;EISSN: 1095-9203 ;DOI: 10.1126/science.aat7615 ;PMID: 30545854

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Title:
Integrative functional genomic analysis of human brain development and neuropsychiatric risks
Author: Li, Mingfeng ; Santpere, Gabriel ; Imamura Kawasawa, Yuka ; Evgrafov, Oleg V ; Gulden, Forrest O ; Pochareddy, Sirisha ; Sunkin, Susan M ; Li, Zhen ; Shin, Yurae ; Zhu, Ying ; Sousa, André M M ; Werling, Donna M ; Kitchen, Robert R ; Kang, Hyo Jung ; Pletikos, Mihovil ; Choi, Jinmyung ; Muchnik, Sydney ; Xu, Xuming ; Wang, Daifeng ; Lorente-Galdos, Belen ; Liu, Shuang ; Giusti-Rodríguez, Paola ; Won, Hyejung ; de Leeuw, Christiaan A ; Pardiñas, Antonio F ; Hu, Ming ; Jin, Fulai ; Li, Yun ; Owen, Michael J ; O'Donovan, Michael C ; Walters, James T R ; Posthuma, Danielle ; Reimers, Mark A ; Levitt, Pat ; Weinberger, Daniel R ; Hyde, Thomas M ; Kleinman, Joel E ; Geschwind, Daniel H ; Hawrylycz, Michael J ; State, Matthew W ; Sanders, Stephan J ; Sullivan, Patrick F ; Gerstein, Mark B ; Lein, Ed S ; Knowles, James A ; Sestan, Nenad
Subjects: Adolescents ; Brain ; Brain - embryology ; Brain - growth & development ; Children ; Cognition ; Convergence ; Dendritic structure ; Deoxyribonucleic acid ; Disorders ; Disruption ; DNA ; DNA methylation ; Embryogenesis ; Embryonic growth stage ; Epigenesis, Genetic ; Epigenetics ; Epigenomics ; Etiology ; Fetuses ; Gene expression ; Gene Expression Regulation, Developmental ; Gene regulation ; Gene Regulatory Networks ; Genes ; Genomic analysis ; Health risks ; Human behavior ; Humans ; Medicin och hälsovetenskap ; Mental disorders ; Mental Disorders - genetics ; Modules ; Myelination ; Neocortex ; Nervous System Diseases - genetics ; Neurodevelopmental disorders ; Neurogenesis - genetics ; Oligodendrocytes ; Regional analysis ; Regional development ; Single-Cell Analysis ; Transcription ; Transcriptome
Is Part Of: Science (American Association for the Advancement of Science), 2018-12, Vol.362 (6420), p.1264
Description: 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 , , , , and ) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
Publisher: United States: The American Association for the Advancement of Science
Language: English
Identifier: ISSN: 0036-8075
ISSN: 1095-9203
EISSN: 1095-9203
DOI: 10.1126/science.aat7615
PMID: 30545854
Source: SWEPUB Freely available online

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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

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