作者
Menachem Fromer, Panos Roussos, Solveig K Sieberts, Jessica S Johnson, David H Kavanagh, Thanneer M Perumal, Douglas M Ruderfer, Edwin C Oh, Aaron Topol, Hardik R Shah, Lambertus L Klei, Robin Kramer, Dalila Pinto, Zeynep H Gümüş, A Ercument Cicek, Kristen K Dang, Andrew Browne, Cong Lu, Lu Xie, Ben Readhead, Eli A Stahl, Jianqiu Xiao, Mahsa Parvizi, Tymor Hamamsy, John F Fullard, Ying-Chih Wang, Milind C Mahajan, Jonathan MJ Derry, Joel T Dudley, Scott E Hemby, Benjamin A Logsdon, Konrad Talbot, Towfique Raj, David A Bennett, Philip L De Jager, Jun Zhu, Bin Zhang, Patrick F Sullivan, Andrew Chess, Shaun M Purcell, Leslie A Shinobu, Lara M Mangravite, Hiroyoshi Toyoshiba, Raquel E Gur, Chang-Gyu Hahn, David A Lewis, Vahram Haroutunian, Mette A Peters, Barbara K Lipska, Joseph D Buxbaum, Eric E Schadt, Keisuke Hirai, Kathryn Roeder, Kristen J Brennand, Nicholas Katsanis, Enrico Domenici, Bernie Devlin, Pamela Sklar
发表日期
2016/11
期刊
Nature neuroscience
卷号
19
期号
11
页码范围
1442-1453
出版商
Nature Publishing Group US
简介
Over 100 genetic loci harbor schizophrenia-associated variants, yet how these variants confer liability is uncertain. The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of people with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, ∼20% of schizophrenia loci have variants that could contribute to altered gene expression and liability. In five loci, only a single gene was involved: FURIN, TSNARE1, CNTN4, CLCN3 or SNAP91. Altering expression of FURIN, TSNARE1 or CNTN4 changed neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yielded abnormal migration. Of 693 genes showing significant case-versus-control differential expression, their fold changes were ≤ 1.33, and an independent cohort yielded similar results. Gene co-expression implicates …
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