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Comprehensive functional genomic resource and integrative model for the human brain

Authors
Daifeng Wang,Shuang Liu
Jonathan Warrell,Hyejung Won,Xu Shi,Fábio Navarro,Declan Clarke,Mengting Gu,Prashant Emani,Yucheng Yang,Min Xu,Michael Gandal,Shaoke Lou,Jing Zhang,Jonathan Park,Chengfei Yan,Suhn Rhie,Kasidet Manakongtreecheep,Holly Zhou,Aparna Nathan,Mette Peters,Eugenio Mattei,Dominic Fitzgerald,Tonya Brunetti,Jill Moore,Yan Jiang,Kiran Girdhar,Gabriel Hoffman,Selim Kalaycı,Zeynep Gümüş,Gregory Crawford,Panos Roussos,Schahram Akbarian,Andrew Jaffe,Kevin White,Zhiping Weng,Nenad Šestan,Daniel Geschwind,James Knowles,Mark Gerstein,Allison Ashley‐Koch,Melanie Garrett,Lingyun Song,Alexias Safi,Graham Johnson,Gregory Wray,Timothy Reddy,Fernando Goes,Peter Zandi,Julien Bryois,Amanda Price,Nikolay Ivanov,Leonardo Collado‐Torres,Thomas Hyde,Emily Burke,Joel Kleiman,Ran Tao,Joo Shin,Marija Kundaković,Leanne Brown,Bibi Kassim,Royce Park,Jennifer Wiseman,Elizabeth Zharovsky,Rivka Jacobov,Olivia Devillers,Elie Flatow,Barbara Lipska,David Lewis,Vahram Haroutunian,Chang-Gyu Hahn,Alexander Charney,Stella Dracheva,Alexey Kozlenkov,Judson Belmont,Diane Valle,Nancy Francoeur,Evi Hadjimichael,Dalila Pinto,Harm Bakel,John Fullard,Jaroslav Bendl,Mads Hauberg,Lara Mangravite,Younbyoung Chae,Junmin Peng,Mingming Niu,Xusheng Wang,Maree Webster,Thomas Beach,Chao Chen,Yi Jiang,Rujia Dai,Annie Shieh,Chunyu Liu,Kay Grennan,Yan Xia,Ramu Vadukapuram,Yongjun Wang,Lijun Cheng,Miguel Brown,Mimi Brown,Thomas Goodman,Majd Alsayed,Damon Polioudakis,Brie Wamsley,Jiani Yin,Tarik Hadžić,Luis Torre-Ubieta,Vivek Swarup,Stephan Sanders,Matthew State,Donna Werling,Joon‐Yong An,Brooke Sheppard,A. Willsey,Mohana Ray,Gina Giase,Amira Kefi,Michael Purcaro,Henry Pratt,Jack Huey,Tyler Borrman,Patrick Sullivan,Paola Giusti‐Rodríguez,Yunjung Kim,Jin Szatkiewicz,Christoper Armoskus,Adrian Camarena,Peggy Farnham,Valeria Spitsyna,Heather Witt,Shannon Schreiner,Oleg Evgrafov,Robert Kitchen,Gamze Gürsoy,Becky Carlyle,Angus Nairn,Mingfeng Li,Sirisha Pochareddy,Mario Škarica,Zhen Li,André Sousa,Gabriel Santpere,Jinmyung Choi,Ying Zhu,Tianliuyun Gao,Daniel Miller,Adriana Cherskov,Mo Yang,Anahita Amiri,Gianfilippo Coppola,Jessica Mariani,Soraya Scuderi,Anna Szekely,Flora Vaccarino,Feinan Wu,Sherman Weissman,Tanmoy Roychowdhury
+157 authors
,Alexej Abyzov
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Published
Dec 13, 2018
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Abstract

Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.

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