Integrative functional genomic analysis of human brain development and neuropsychiatric risks.
Mingfeng LiGabriel Santpere BaróYuka Imamura KawasawaOleg V EvgrafovForrest O GuldenSirisha PochareddySusan M SunkinZhen LiYurae ShinYing ZhuAndré M M SousaDonna M WerlingRobert R KitchenHyo Jung KangMihovil PletikosJinmyung ChoiSydney MuchnikXuming XuDaifeng WangBelen Lorente-GaldosShuang LiuPaola Giusti-RodríguezHyejung WonChristiaan A de LeeuwAntonio F Pardinasnull nullnull nullnull nullMing HuFulai JinYun LiMichael J OwenMichael C O'DonovanJames T R WaltersDanielle PosthumaMark A ReimersPat LevittDaniel R WeinbergerThomas M HydeJoel E KleinmanDaniel H GeschwindMichael J HawrylyczMatthew W StateStephan J SandersPatrick F SullivanMark B GersteinEd S LeinJames A KnowlesNenad SestanPublished in: Science (New York, N.Y.) (2019)
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.