| Literature DB >> 27668389 |
Menachem Fromer1,2, Panos Roussos1,2,3,4, Solveig K Sieberts5, Jessica S Johnson1, David H Kavanagh1,2, Thanneer M Perumal5, Douglas M Ruderfer1,2, Edwin C Oh6,7, Aaron Topol1, Hardik R Shah2, Lambertus L Klei8, Robin Kramer9, Dalila Pinto1,2,3,10, Zeynep H Gümüş2, A Ercument Cicek11, Kristen K Dang5, Andrew Browne3,10, Cong Lu12, Lu Xie12, Ben Readhead2, Eli A Stahl1,2, Jianqiu Xiao6, Mahsa Parvizi6, Tymor Hamamsy1,2, John F Fullard1, Ying-Chih Wang2, Milind C Mahajan2, Jonathan M J Derry5, Joel T Dudley2, Scott E Hemby13, Benjamin A Logsdon5, Konrad Talbot14, Towfique Raj2,15,16, David A Bennett17, Philip L De Jager16,18, Jun Zhu2, Bin Zhang2, Patrick F Sullivan19,20, Andrew Chess2,3,21, Shaun M Purcell1,2, Leslie A Shinobu22, Lara M Mangravite5, Hiroyoshi Toyoshiba23, Raquel E Gur24, Chang-Gyu Hahn25, David A Lewis8, Vahram Haroutunian1,4,15, Mette A Peters5, Barbara K Lipska9, Joseph D Buxbaum1,3,10, Eric E Schadt2, Keisuke Hirai22, Kathryn Roeder11,12, Kristen J Brennand1,3,15, Nicholas Katsanis6,26, Enrico Domenici27, Bernie Devlin8,28, Pamela Sklar1,2,3.
Abstract
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 a network relevant for schizophrenia. Our findings show that schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.Entities:
Mesh：
Year: 2016 PMID： 27668389 PMCID： PMC5083142 DOI： 10.1038/nn.4399
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884