TY - JOUR
T1 - Integrative functional genomic analysis of human brain development and neuropsychiatric risks
AU - Li, Mingfeng
AU - Santpere, Gabriel
AU - Kawasawa, Yuka Imamura
AU - Evgrafov, Oleg V.
AU - Gulden, Forrest O.
AU - Pochareddy, Sirisha
AU - Sunkin, Susan M.
AU - Li, Zhen
AU - Shin, Yurae
AU - Zhu, Ying
AU - Sousa, André M.M.
AU - Werling, Donna M.
AU - Kitchen, Robert R.
AU - Kang, Hyo Jung
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.
AU - Hu, Ming
AU - Jin, Fulai
AU - Li, Yun
AU - Owen, Michael J.
AU - O'Donovan, Michael C.
AU - Walters, James T.R.
AU - Posthuma, Danielle
AU - Levitt, Pat
AU - Weinberger, Daniel R.
AU - Hyde, Thomas M.
AU - Kleinman, Joel E.
AU - Geschwind, Daniel H.
AU - Hawrylycz, Michael J.
AU - State, Matthew W.
AU - Sanders, Stephan J.
AU - Sullivan, Patrick F.
AU - Gerstein, Mark B.
AU - Lein, Ed S.
AU - Knowles, James A.
AU - Sestan, Nenad
PY - 2018/12/14
Y1 - 2018/12/14
N2 - 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=85058377382&partnerID=8YFLogxK
U2 - 10.1126/science.aat7615
DO - 10.1126/science.aat7615
M3 - Article
C2 - 30545854
AN - SCOPUS:85058377382
SN - 0036-8075
VL - 362
SP - 1
EP - 15
JO - Science
JF - Science
IS - 6420
M1 - 1264
ER -
