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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

by Hadjimichael, Evi , Mane, Shrikant , Levitt, Pat , Olson, Eric , Polioudakis, Damon , Xu, Min , Wu, Feinan , Pochareddy, Sirisha , Dee, Nick , Fitzgerald, Dominic , Kaur, Navjot , Gittin, Reaghan , Moore, Jill , Warrell, Jonathan , Sedmak, Goran , Kitchen, Robert R. , Wohnoutka, Paul , Sanders, Stephan J. , Yoon, Hee Jae , DelValle, Diane , Mason, Christopher E. , Lee, Felix , Parikshak, Neelroop , Sandman, David , Fulfs, Erich , Weng, Zhiping , Hawrylycz, Michael J. , Sjoquist, Nathan , Chae, Yooree , O’Donovan, Michael C. , Abyzov, Alexej , Kuan, Chihchau L. , Hahn, Chang-Gyu , Evgrafov, Oleg V. , Bernard, Amy , Giusti-Rodríguez, Paola , Gürsoy, Gamze , Parker, Patrick D. , White, Kevin P. , Gee, Garrett , Hauberg, Mads E. , Gulden, Forrest O. , Amiri, Anahita , Johnson, Matthew B. , Mariani, Jessica , Riley, Zack L. , Shen, Elaine H. , Deelman, Ewa , Gourley, Lindsey , van Bakel, Harm , Roll, Katie , Wang, Daifeng , Mayani, Rajiv , Lemon, Tracy A. , Wiseman, Jennifer R. , Caldejon, Shiella , Mattei, Eugenio , Gao, Tianliuyun , Kleinman, Joel E. , Aiona, Kaylynn , Franjic, Daniel , Giase, Gina , Shin, Joo Heon , Dai, Rujia , Smith, Michael , Bennet, Crissa , Price, Amanda J. , Sto

in 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 / Genetics / Genomic analysis / Genomics / Health risks / Human behavior / Humans / Maturation / Mental disorders / Mental Disorders - genetics / Meta Analysis / Modules / Myelination / Neocortex / Nervous System Diseases - genetics / Neurodevelopmental disorders / Neurogenesis - genetics / Oligodendrocytes / Regional analysis / Regional development / Single-Cell Analysis / Synapses / Transcription / Transcriptome

2018

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2018

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2018

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Journal Article

Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Hadjimichael, Evi,

Mane, Shrikant,

Levitt, Pat,

Olson, Eric,

Polioudakis, Damon,

Xu, Min,

Wu, Feinan,

Pochareddy, Sirisha,

Dee, Nick,

Fitzgerald, Dominic,

Kaur, Navjot,

Gittin, Reaghan,

Moore, Jill,

Warrell, Jonathan,

Sedmak, Goran,

Kitchen, Robert R.,

Wohnoutka, Paul,

Sanders, Stephan J.,

Yoon, Hee Jae,

DelValle, Diane,

Mason, Christopher E.,

Lee, Felix,

Parikshak, Neelroop,

Sandman, David,

Fulfs, Erich,

Weng, Zhiping,

Hawrylycz, Michael J.,

Sjoquist, Nathan,

Chae, Yooree,

O’Donovan, Michael C.,

Abyzov, Alexej,

Kuan, Chihchau L.,

Hahn, Chang-Gyu,

Evgrafov, Oleg V.,

Bernard, Amy,

Giusti-Rodríguez, Paola,

Gürsoy, Gamze,

Parker, Patrick D.,

White, Kevin P.,

Gee, Garrett,

Hauberg, Mads E.,

Gulden, Forrest O.,

Amiri, Anahita,

Johnson, Matthew B.,

Mariani, Jessica,

Riley, Zack L.,

Shen, Elaine H.,

Deelman, Ewa,

Gourley, Lindsey,

van Bakel, Harm,

Roll, Katie,

Wang, Daifeng,

Mayani, Rajiv,

Lemon, Tracy A.,

Wiseman, Jennifer R.,

Caldejon, Shiella,

Mattei, Eugenio,

Gao, Tianliuyun,

Kleinman, Joel E.,

Aiona, Kaylynn,

Franjic, Daniel,

Giase, Gina,

Shin, Joo Heon,

Dai, Rujia,

Smith, Michael,

Bennet, Crissa,

Price, Amanda J.,

Sto

2018

Overview

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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Publisher

The American Association for the Advancement of Science

Subject

Adolescents

/ Brain

/ Brain - embryology

/ Brain - growth & development

/ Children

/ Cognition

/ Convergence