Comprehensive functional genomic resource and integrative model for the human brain

作者：Daifeng Wang, Shuang Liu, Jonathan Warrell, Hyejung Won, Xu Shi, Fábio C. P. Navarro, Declan Clarke, Mengting Gu, Prashant S. Emani, Yucheng Yang, Min Xu, Michael J. Gandal, Shaoke Lou, Jing Zhang, Jonathan J. Park, Chengfei Yan, Suhn K. Rhie, Kasidet Manakongtreecheep, Holly Zhou, Aparna Nathan, Mette A. Peters, Eugenio Mattei, Dominic Fitzgerald, Tonya M. Brunetti, Jill E. Moore, Yan Jiang, Kiran Girdhar, Gabriel E. Hoffman, Selim Kalaycı, Zeynep H. Gümüş, Gregory E. Crawford, Panos Roussos, Schahram Akbarian, Andrew E. Jaffe, Kevin P. White, Zhiping Weng, Nenad Šestan, Daniel H. Geschwind, James A. Knowles, Mark Gerstein, Allison E. Ashley‐Koch, Gregory E. Crawford, Melanie E. Garrett, Lingyun Song, Alexias Safi, Graham D. Johnson, Gregory A. Wray, Timothy E. Reddy, Fernando S. Goes, Peter P. Zandi, Julien Bryois, Andrew E. Jaffe, Amanda J. Price, Nikolay A. Ivanov, Leonardo Collado‐Torres, Thomas M. Hyde, Emily E. Burke, Joel E. Kleiman, Ran Tao, Joo Heon Shin, Schahram Akbarian, Kiran Girdhar, Yan Jiang, Marija Kundaković, Leanne Brown, Bibi Kassim, Royce Park, Jennifer Wiseman, Elizabeth Zharovsky, Rivka Jacobov, Olivia Devillers, Elie Flatow, Gabriel E. Hoffman, Barbara K. Lipska, David A. Lewis, Vahram Haroutunian, Chang-Gyu Hahn, Alexander W. Charney, Stella Dracheva, Alexey Kozlenkov, Judson Belmont, Diane M. Del Valle, Nancy Francoeur, Evi Hadjimichael, Dalila Pinto, Harm van Bakel, Panos Roussos, John F. Fullard, Jaroslav Bendl, Mads E. Hauberg, Lara M. Mangravite, Mette A. Peters, Yooree Chae, Junmin Peng, Mingming Niu, Xusheng Wang, Maree J. Webster, Thomas G. Beach, Chao Chen, Yi Jiang, Rujia Dai, Annie W. Shieh, Chunyu Liu, Kay Grennan, Yan Xia, Ramu Vadukapuram, Yongjun Wang, Dominic Fitzgerald, Lijun Cheng, Miguel Brown, Mimi Brown, Tonya M. Brunetti, Thomas Goodman, Majd Alsayed, Michael J. Gandal, Daniel H. Geschwind, Hyejung Won, Damon Polioudakis, Brie Wamsley, Jiani Yin, Tarik Hadžić, Luis de la Torre-Ubieta, Vivek Swarup, Stephan Sanders, Matthew W. State, Donna M. Werling, Joon‐Yong An, Brooke Sheppard, A. Jeremy Willsey, Kevin P. White, Mohana Ray, Gina Giase, Amira Kefi, Eugenio Mattei, Michael Purcaro, Zhiping Weng, Jill E. Moore, Henry Pratt, Jack Huey, Tyler Borrman, Patrick F. Sullivan, Paola Giusti‐Rodríguez, Yunjung Kim, Patrick Sullivan, Jin Szatkiewicz, Suhn K. Rhie, Christoper Armoskus, Adrian Camarena, Peggy Farnham, Valeria N. Spitsyna, Heather Witt, Shannon Schreiner, Oleg V. Evgrafov, James A. Knowles, Mark Gerstein, Shuang Liu, Daifeng Wang, Fábio C. P. Navarro, Jonathan Warrell, Declan Clarke, Prashant S. Emani, Mengting Gu, Xu Shi, Min Xu, Yucheng Yang, Robert R. Kitchen, Gamze Gürsoy, Jing Zhang, Becky C. Carlyle, Angus C. Nairn, Mingfeng Li, Sirisha Pochareddy, Nenad Šestan, Mario Škarica, Zhen Li, André M. M. Sousa, Gabriel Santpere, Jinmyung Choi, Ying Zhu, Tianliuyun Gao, Daniel J. Miller, Adriana Cherskov, Mo Yang, Anahita Amiri, Gianfilippo Coppola, Jessica Mariani, Soraya Scuderi, Anna Szekely, Flora M. Vaccarino, Feinan Wu, Sherman M. Weissman, Tanmoy Roychowdhury, Alexej Abyzov · 发表于：Science · 年份：2018 · DOI：10.1126/science.aat8464 · 被引用次数：1103 · 研究领域：Genetic Associations and Epidemiology、Single-cell and spatial transcriptomics、Epigenetics and DNA Methylation

INTRODUCTION Strong genetic associations have been found for a number of psychiatric disorders. However, understanding the underlying molecular mechanisms remains challenging. RATIONALE To address this challenge, the PsychENCODE Consortium has developed a comprehensive online resource and integrative models for the functional genomics of the human brain. RESULTS The base of the pyramidal resource is the datasets generated by PsychENCODE, including bulk transcriptome, chromatin, genotype, and Hi-C datasets and single-cell transcriptomic data from ~32,000 cells for major brain regions. We have merged these with data from Genotype-Tissue Expression (GTEx), ENCODE, Roadmap Epigenomics, and single-cell analyses. Via uniform processing, we created a harmonized resource, allowing us to survey functional genomics data on the brain over a sample size of 1866 individuals. From this uniformly processed dataset, we created derived data products. These include lists of brain-expressed genes, coexpression modules, and single-cell expression profiles for many brain cell types; ~79,000 brain-active enhancers with associated Hi-C loops and topologically associating domains; and ~2.5 million expression quantitative-trait loci (QTLs) comprising ~238,000 linkage-disequilibrium–independent single-nucleotide polymorphisms and of other types of QTLs associated with splice isoforms, cell fractions, and chromatin activity. By using these, we found that >88% of the cross-population variation in brain ...