Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Li, Mingfeng; Santpere, Gabriel; Kawasawa, Yuka Imamura; Evgrafov, Oleg V.; Gulden, Forrest O.; Pochareddy, Sirisha; Sunkin, Susan M.; Li, Zhen; Shin, Yurae; Zhu, Ying; Sousa, Andre 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-Rodriguez, Paola; Won, Hyejung; de Leeuw, Christiaan A.; Pardinas, Antonio F.; Hu, Ming; Jin, Fulai; Li, Yun; Owen, Michael J.; O'Donovan, Michael C.; Walters, James T. R.; Posthuma, Danielle; 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

doi:10.1126/science.aat7615

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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Li, Mingfeng;
Santpere, Gabriel;
Kawasawa, Yuka Imamura;
Evgrafov, Oleg V.;
Gulden, Forrest O.;
... Kang, Hyo Jung;
외 39명

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초록

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.

키워드

SINGLE-CELL ANALYSIS; DE-NOVO MUTATIONS; DNA METHYLATION; SUSCEPTIBILITY LOCI; EXPRESSION ANALYSIS; MENTAL-RETARDATION; READ ALIGNMENT; TRANSCRIPTOME; ASSOCIATION; ARCHITECTURE

제목: Integrative functional genomic analysis of human brain development and neuropsychiatric risks

저자: Li, Mingfeng; Santpere, Gabriel; Kawasawa, Yuka Imamura; Evgrafov, Oleg V.; Gulden, Forrest O.; Pochareddy, Sirisha; Sunkin, Susan M.; Li, Zhen; Shin, Yurae; Zhu, Ying; Sousa, Andre 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-Rodriguez, Paola; Won, Hyejung; de Leeuw, Christiaan A.; Pardinas, Antonio F.; Hu, Ming; Jin, Fulai; Li, Yun; Owen, Michael J.; O'Donovan, Michael C.; Walters, James T. R.; Posthuma, Danielle; 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

DOI: 10.1126/science.aat7615

발행일: 2018-12

유형: Article

저널명: Science

권: 362

호: 6420

페이지: 1264 ~ +

언어: ENG

출판사: AMER ASSOC ADVANCEMENT SCIENCE

발행국가: 미국

ISSN: E 1095-9203
P 0036-8075

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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

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