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Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Author(s) -

Mingfeng Li,

Gabriel Santpere,

Yuka Imamura Kawasawa,

Oleg V. Evgrafov,

Forrest O. Gulden,

Sirisha Pochareddy,

Susan M. Sunkin,

Zhen Li,

Yurae Shin,

Ying Zhu,

André M. M. Sousa,

Donna M. Werling,

Robert R. Kitchen,

Hyo Jung Kang,

Mihovil Pletikos,

Jinmyung Choi,

Sydney Muchnik,

Xuming Xu,

Daifeng Wang,

Belén Lorente-Galdós,

Shuang Liu,

Paola GiustiRodríguez,

Hyejung Won,

Christiaan de Leeuw,

Antonio F. Pardiñas,

Ming Hu,

Fulai Jin,

Yun Li,

Michael J. Owen,

Michael O’Donovan,

James Walters,

Daniëlle Posthuma,

Mark A. Reimers,

Pat Levitt,

Daniel R. Weinberger,

Thomas M. Hyde,

Joel E. Kleinman,

Daniel H. Geschwind,

Michael Hawrylycz,

Matthew W. State,

Stephan Sanders,

Patrick F. Sullivan,

Mark Gerstein,

Ed S. Lein,

James A. Knowles,

Nenad Šestan,

A. Jeremy Willsey,

Aaron Oldre,

Aaron Szafer,

Adrian Camarena,

Adriana Cherskov,

Alexander W. Charney,

Alexej Abyzov,

Alexey Kozlenkov,

Alexias Safi,

Allan R. Jones,

Allison E. AshleyKoch,

Amanda Ebbert,

Amanda J. Price,

Amanda Sekijima,

Amira Kefi,

Amy Bernard,

Anahita Amiri,

Andrea Sboner,

Andrew E. Clark,

Andrew E. Jaffe,

Andrew T.N. Tebbenkamp,

Andy J. Sodt,

Angie GuillozetBongaarts,

Angus C. Nairn,

Anita Carey,

Anita Hüttner,

Ann Chervenak,

Anna Szekely,

Annie W. Shieh,

Arif Harmanci,

Barbara K. Lipska,

Becky C. Carlyle,

Ben W. Gregor,

Bibi Kassim,

Brooke Sheppard,

Candace Bichsel,

Chang-Gyu Hahn,

Chang-Kyu Lee,

Chao Chen,

Chihchau L. Kuan,

Chinh Dang,

Chris Lau,

Christine Cuhaciyan,

Christoper Armoskus,

Christopher E. Mason,

Chunyu Liu,

Cliff Slaughterbeck,

Crissa Bennet,

Dalila Pinto,

Damon Polioudakis,

Daniel Franjic,

Daniel J. Miller,

Darren Bertagnolli,

David A. Lewis,

David Feng,

David Sandman,

Declan Clarke,

Derric Williams,

Diane M. Del Valle,

Dominic Fitzgerald,

Elaine Shen,

Elie Flatow,

Elizabeth Zharovsky,

Emily E. Burke,

Eric C. Olson,

Erich Fulfs,

Eugenio Mattei,

Evi Hadjimichael,

Ewa Deelman,

Fábio C. P. Navarro,

Feinan Wu,

Felix Lee,

Feng Cheng,

Fernando S. Goes,

Flora M. Vaccarino,

Fuchen Liu,

Gabriel E. Hoffman,

Gamze Gürsoy,

Garrett Gee,

Gaurang Mehta,

Gianfilippo Coppola,

Gina Giase,

Goran Sedmak,

Graham D. Johnson,

Gregory A. Wray,

Gregory E. Crawford,

Guangyu Gu,

Harm van Bakel,

Heather Witt,

Hee Jae Yoon,

Henry Pratt,

Hongyu Zhao,

Ian Glass,

Jack Huey,

James M. Arnold,

James P. Noonan,

Jaroslav Bendl,

Jayson M. Jochim,

Jeff Goldy,

Jennifer Herstein,

Jennifer Wiseman,

Jeremy A. Miller,

Jessica Mariani,

Jessica Stoll,

J. Russell Moore,

Jin Szatkiewicz,

Jing Leng,

Jing Zhang,

Jody Parente,

Joel Rozowsky,

John F. Fullard,

John G. Hohmann,

John C. Morris,

John W. Phillips,

Jonathan Warrell,

Joo Heon Shin,

JoonYong An,

Judson Belmont,

Julie Nyhus,

Julie Pendergraft,

Julien Bryois,

Katie Roll,

Kay Grennan,

Kaylynn Aiona,

Kevin P. White,

Kimberly A. Aldinger,

Kimberly A. Smith,

Kiran Girdhar,

Kristina Brouner,

Lara M. Mangravite,

Leanne Brown,

Leonardo ColladoTorres,

Lijun Cheng,

Lindsey Gourley,

Lingyun Song,

Luis de la Torre-Ubieta,

Lukas Habegger,

Lydia Ng,

Mads E. Hauberg,

Marco Onorati,

Maree J. Webster,

Marija Kundaković,

Mario Škarica,

Mark Reimers,

Matthew B. Johnson,

Maxine Chen,

Melanie E. Garrett,

Melanie Sarreal,

Melissa Reding,

Mengting Gu,

Mette A. Peters,

Michael Fisher,

Michael J. Gandal,

Michael Purcaro,

Michael W. Smith,

Miguel Brown,

Mikihito Shibata,

Mimi Brown,

Min Xu,

Mo Yang,

Mohana Ray,

Nadiya V. Shapovalova,

Nancy Francoeur,

Nathan Sjoquist,

Naveed Mastan,

Navjot Kaur,

Neelroop Parikshak,

Nerick F. Mosqueda,

Nhan-Kiet Ngo,

Nick Dee,

Nikolay A. Ivanov,

Olivia Devillers,

Panos Roussos,

Patrick D. Parker,

Paul Manser,

Paul Wohnoutka,

Peggy Farnham,

Peter P. Zandi,

Prashant S. Emani,

Rachel Dalley,

Rajiv Mayani,

Ran Tao,

Reaghan Gittin,

Richard E. Straub,

Richard P. Lifton,

Rivka Jacobov,

Robert Howard,

Royce Park,

Rujia Dai,

Sandra Abramowicz,

Schahram Akbarian,

Shan Schreiner,

Shaojie Ma,

Sheana Parry,

Sheila Shapouri,

Sherman M. Weissman,

Shiella Caldejon,

Shrikant Mane,

SongLin Ding,

Soraya Scuderi,

Stella Dracheva,

Stephanie Butler,

Steven Lisgo,

Suhn K. Rhie,

Susan Lindsay,

Suvro Datta,

Tade Souaiaia,

Tanmoy Roychowdhury,

Teresa García Gómez,

Theresa Naluai-Cecchini,

Thomas G. Beach,

Thomas Goodman,

Tianliuyun Gao,

Tim Dolbeare,

Tim Fliss,

Timothy E. Reddy,

Ting Chen,

Tom M. Hyde,

Tonya M. Brunetti,

Tracy Lemon,

Tsega Desta,

Tyler Borrman,

Vahram Haroutunian,

Valeria N. Spitsyna,

Vivek Swarup,

Xu Shi,

Yan Jiang,

Yan Xia,

Yang-Ho Chen,

Yi Jiang,

Yongjun Wang,

Yooree Chae,

Yucheng Yang,

Yunjung Kim,

Zack L. Riley,

Željka Krsnik,

Zemin Deng,

Zhiping Weng,

Zhixiang Lin,

Zhuo Li

Publication year - 2018

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aat7615

Subject(s) - transcriptome , biology , neuroscience , human brain , epigenomics , epigenetics , context (archaeology) , dna methylation , epigenome , gene , genetics , gene expression , paleontology

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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