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Integrative functional genomic analysis of human brain development and neuropsychiatric risks
- Li, Mingfeng;
- Santpere, Gabriel;
- Imamura Kawasawa, Yuka;
- Evgrafov, Oleg V;
- Gulden, Forrest O;
- Pochareddy, Sirisha;
- Sunkin, Susan M;
- Li, Zhen;
- Shin, Yurae;
- Zhu, Ying;
- Sousa, André MM;
- Werling, Donna M;
- Kitchen, Robert R;
- Kang, Hyo Jung;
- Pletikos, Mihovil;
- Choi, Jinmyung;
- Muchnik, Sydney;
- Xu, Xuming;
- Wang, Daifeng;
- Lorente-Galdos, Belen;
- Liu, Shuang;
- Giusti-Rodríguez, Paola;
- Won, Hyejung;
- de Leeuw, Christiaan A;
- Pardiñas, Antonio F;
- Hu, Ming;
- Jin, Fulai;
- Li, Yun;
- Owen, Michael J;
- O’Donovan, Michael C;
- Walters, James TR;
- Posthuma, Danielle;
- Reimers, Mark A;
- Levitt, Pat;
- Weinberger, Daniel R;
- Hyde, Thomas M;
- Kleinman, Joel E;
- Geschwind, Daniel H;
- Hawrylycz, Michael J;
- State, Matthew W;
- Sanders, Stephan J;
- Sullivan, Patrick F;
- Gerstein, Mark B;
- Lein, Ed S;
- Knowles, James A;
- Sestan, Nenad;
- Willsey, A Jeremy;
- Oldre, Aaron;
- Szafer, Aaron;
- Camarena, Adrian;
- Cherskov, Adriana;
- Charney, Alexander W;
- Abyzov, Alexej;
- Kozlenkov, Alexey;
- Safi, Alexias;
- Jones, Allan R;
- Ashley-Koch, Allison E;
- Ebbert, Amanda;
- Price, Amanda J;
- Sekijima, Amanda;
- Kefi, Amira;
- Bernard, Amy;
- Amiri, Anahita;
- Sboner, Andrea;
- Clark, Andrew;
- Jaffe, Andrew E;
- Tebbenkamp, Andrew TN;
- Sodt, Andy J;
- Guillozet-Bongaarts, Angie L;
- Nairn, Angus C;
- Carey, Anita;
- Huttner, Anita;
- Chervenak, Ann;
- Szekely, Anna;
- Shieh, Annie W;
- Harmanci, Arif;
- Lipska, Barbara K;
- Carlyle, Becky C;
- Gregor, Ben W;
- Kassim, Bibi S;
- Sheppard, Brooke;
- Bichsel, Candace;
- Hahn, Chang-Gyu;
- Lee, Chang-Kyu;
- Chen, Chao;
- Kuan, Chihchau L;
- Dang, Chinh;
- Lau, Chris;
- Cuhaciyan, Christine;
- Armoskus, Christoper;
- Mason, Christopher E;
- Liu, Chunyu;
- Slaughterbeck, Cliff R;
- Bennet, Crissa;
- Pinto, Dalila;
- Polioudakis, Damon;
- Franjic, Daniel;
- Miller, Daniel J;
- Bertagnolli, Darren;
- Lewis, David A;
- Feng, David;
- Sandman, David;
- Clarke, Declan;
- Williams, Derric;
- DelValle, Diane;
- Fitzgerald, Dominic;
- Shen, Elaine H;
- Flatow, Elie;
- Zharovsky, Elizabeth;
- Burke, Emily E;
- Olson, Eric;
- Fulfs, Erich;
- Mattei, Eugenio;
- Hadjimichael, Evi;
- Deelman, Ewa;
- Navarro, Fabio CP;
- Wu, Feinan;
- Lee, Felix;
- Cheng, Feng;
- Goes, Fernando S;
- Vaccarino, Flora M;
- Liu, Fuchen;
- Hoffman, Gabriel E;
- Gürsoy, Gamze;
- Gee, Garrett;
- Mehta, Gaurang;
- Coppola, Gianfilippo;
- Giase, Gina;
- Sedmak, Goran;
- Johnson, Graham D;
- Wray, Gregory A;
- Crawford, Gregory E;
- Gu, Guangyu;
- van Bakel, Harm;
- Witt, Heather;
- Yoon, Hee Jae;
- Pratt, Henry;
- Zhao, Hongyu;
- Glass, Ian A;
- Huey, Jack;
- Arnold, James;
- Noonan, James P;
- Bendl, Jaroslav;
- Jochim, Jayson M;
- Goldy, Jeff;
- Herstein, Jennifer;
- Wiseman, Jennifer R;
- Miller, Jeremy A;
- Mariani, Jessica;
- Stoll, Jessica;
- Moore, Jill;
- Szatkiewicz, Jin;
- Leng, Jing;
- Zhang, Jing;
- Parente, Jody;
- Rozowsky, Joel;
- Fullard, John F;
- Hohmann, John G;
- Morris, John;
- Phillips, John W;
- Warrell, Jonathan;
- Shin, Joo Heon;
- An, Joon-Yong;
- Belmont, Judson;
- Nyhus, Julie;
- Pendergraft, Julie;
- Bryois, Julien;
- Roll, Katie;
- Grennan, Kay S;
- Aiona, Kaylynn;
- White, Kevin P;
- Aldinger, Kimberly A;
- Smith, Kimberly A;
- Girdhar, Kiran;
- Brouner, Kristina;
- Mangravite, Lara M;
- Brown, Leanne;
- Collado-Torres, Leonardo;
- Cheng, Lijun;
- Gourley, Lindsey;
- Song, Lingyun;
- Ubieta, Luis De La Torre;
- Habegger, Lukas;
- Ng, Lydia;
- Hauberg, Mads E;
- Onorati, Marco;
- Webster, Maree J;
- Kundakovic, Marija;
- Skarica, Mario;
- Reimers, Mark;
- Johnson, Matthew B;
- Chen, Maxine M;
- Garrett, Melanie E;
- Sarreal, Melanie;
- Reding, Melissa;
- Gu, Mengting;
- Peters, Mette A;
- Fisher, Michael;
- Gandal, Michael J;
- Purcaro, Michael;
- Smith, Michael;
- Brown, Miguel;
- Shibata, Mikihito;
- Brown, Mimi;
- Xu, Min;
- Yang, Mo;
- Ray, Mohana;
- Shapovalova, Nadiya V;
- Francoeur, Nancy;
- Sjoquist, Nathan;
- Mastan, Naveed;
- Kaur, Navjot;
- Parikshak, Neelroop;
- Mosqueda, Nerick F;
- Ngo, Nhan-Kiet;
- Dee, Nick;
- Ivanov, Nikolay A;
- Devillers, Olivia;
- Roussos, Panos;
- Parker, Patrick D;
- Manser, Paul;
- Wohnoutka, Paul;
- Farnham, Peggy J;
- Zandi, Peter;
- Emani, Prashant S;
- Dalley, Rachel A;
- Mayani, Rajiv;
- Tao, Ran;
- Gittin, Reaghan;
- Straub, Richard E;
- Lifton, Richard P;
- Jacobov, Rivka;
- Howard, Robert E;
- Park, Royce B;
- Dai, Rujia;
- Abramowicz, Sandra;
- Akbarian, Schahram;
- Schreiner, Shannon;
- Ma, Shaojie;
- Parry, Sheana E;
- Shapouri, Sheila;
- Weissman, Sherman;
- Caldejon, Shiella;
- Mane, Shrikant;
- Ding, Song-Lin;
- Scuderi, Soraya;
- Dracheva, Stella;
- Butler, Stephanie;
- Lisgo, Steven N;
- Rhie, Suhn Kyong;
- Lindsay, Susan;
- Datta, Suvro;
- Souaiaia, Tade;
- Roychowdhury, Tanmoy;
- Gomez, Teresa;
- Naluai-Cecchini, Theresa;
- Beach, Thomas G;
- Goodman, Thomas;
- Gao, Tianliuyun;
- Dolbeare, Tim A;
- Fliss, Tim;
- Reddy, Timothy E;
- Chen, Ting;
- Hyde, Tom M;
- Brunetti, Tonya;
- Lemon, Tracy A;
- Desta, Tsega;
- Borrman, Tyler;
- Haroutunian, Vahram;
- Spitsyna, Valeria N;
- Swarup, Vivek;
- Shi, Xu;
- Jiang, Yan;
- Xia, Yan;
- Chen, Yang-Ho;
- Jiang, Yi;
- Wang, Yongjun;
- Chae, Yooree;
- Yang, Yucheng T;
- Kim, Yunjung;
- Riley, Zack L;
- Krsnik, Zeljka;
- Deng, Zemin;
- Weng, Zhiping;
- Lin, Zhixiang;
- Li, Zhuo
- et al.
Published Web Location
https://doi.org/10.1126/science.aat7615Abstract
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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