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Science. 2018 Dec 14;362(6420). pii: eaat7615. doi: 10.1126/science.aat7615.

Integrative functional genomic analysis of human brain development and neuropsychiatric risks.

Collaborators (238)

Willsey AJ, Oldre A, Szafer A, Camarena A, Cherskov A, Charney AW, Abyzov A, Kozlenkov A, Safi A, Jones AR, Ashley-Koch AE, Ebbert A, Price AJ, Sekijima A, Kefi A, Bernard A, Amiri A, Sboner A, Clark A, Jaffe AE, Tebbenkamp ATN, Sodt AJ, Guillozet-Bongaarts AL, Nairn AC, Carey A, Huttner A, Chervenak A, Szekely A, Shieh AW, Harmanci A, Lipska BK, Carlyle BC, Gregor BW, Kassim BS, Sheppard B, Bichsel C, Hahn CG, Lee CK, Chen C, Kuan CL, Dang C, Lau C, Cuhaciyan C, Armoskus C, Mason CE, Liu C, Slaughterbeck CR, Bennet C, Pinto D, Polioudakis D, Franjic D, Miller DJ, Bertagnolli D, Lewis DA, Feng D, Sandman D, Clarke D, Williams D, DelValle D, Fitzgerald D, Shen EH, Flatow E, Zharovsky E, Burke EE, Olson E, Fulfs E, Mattei E, Hadjimichael E, Deelman E, Navarro FCP, Wu F, Lee F, Cheng F, Goes FS, Vaccarino FM, Liu F, Hoffman GE, Gürsoy G, Gee G, Mehta G, Coppola G, Giase G, Sedmak G, Johnson GD, Wray GA, Crawford GE, Gu G, van Bakel H, Witt H, Yoon HJ, Pratt H, Zhao H, Glass IA, Huey J, Arnold J, Noonan JP, Bendl J, Jochim JM, Goldy J, Herstein J, Wiseman JR, Miller JA, Mariani J, Stoll J, Moore J, Szatkiewicz J, Leng J, Zhang J, Parente J, Rozowsky J, Fullard JF, Hohmann JG, Morris J, Phillips JW, Warrell J, Shin JH, An JY, Belmont J, Nyhus J, Pendergraft J, Bryois J, Roll K, Grennan KS, Aiona K, White KP, Aldinger KA, Smith KA, Girdhar K, Brouner K, Mangravite LM, Brown L, Collado-Torres L, Cheng L, Gourley L, Song L, Ubieta LT, Habegger L, Ng L, Hauberg ME, Onorati M, Webster MJ, Kundakovic M, Skarica M, Johnson MB, Chen MM, Garrett ME, Sarreal M, Reding M, Gu M, Peters MA, Fisher M, Gandal MJ, Purcaro M, Smith M, Brown M, Shibata M, Brown M, Xu M, Yang M, Ray M, Shapovalova NV, Francoeur N, Sjoquist N, Mastan N, Kaur N, Parikshak N, Mosqueda NF, Ngo NK, Dee N, Ivanov NA, Devillers O, Roussos P, Parker PD, Manser P, Wohnoutka P, Farnham PJ, Zandi P, Emani PS, Dalley RA, Mayani R, Tao R, Gittin R, Straub RE, Lifton RP, Jacobov R, Howard RE, Park RB, Dai R, Abramowicz S, Akbarian S, Schreiner S, Ma S, Parry SE, Shapouri S, Weissman S, Caldejon S, Mane S, Ding SL, Scuderi S, Dracheva S, Butler S, Lisgo SN, Rhie SK, Lindsay S, Datta S, Souaiaia T, Roychowdhury T, Gomez T, Naluai-Cecchini T, Beach TG, Goodman T, Gao T, Dolbeare TA, Fliss T, Reddy TE, Chen T, Brunetti T, Lemon TA, Desta T, Borrman T, Haroutunian V, Spitsyna VN, Swarup V, Shi X, Jiang Y, Xia Y, Chen YH, Jiang Y, Wang Y, Chae Y, Yang YT, Kim Y, Riley ZL, Krsnik Z, Deng Z, Weng Z, Lin Z, Li Z.

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Contributed equally

Abstract

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.

PMID:
30545854
DOI:
10.1126/science.aat7615
[Indexed for MEDLINE]

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