Fromer, MenachemRoussos, PanosSieberts, Solveig KJohnson, Jessica SKavanagh, David HPerumal, Thanneer MRuderfer, Douglas MOh, Edwin CTopol, AaronShah, Hardik RKlei, Lambertus LKramer, RobinPinto, DalilaGümüş, Zeynep HCicek, A. ErcumentDang, Kristen KBrowne, AndrewLu, CongXie, LuReadhead, BenStahl, Eli AParvizi, MahsaHamamsy, TymorFullard, John FWang, Ying-ChihMahajan, Milind CDerry, Jonathan M JDudley, JoelHemby, Scott ELogsdon, Benjamin ATalbot, KonradRaj, TowfiqueBennett, David ADe Jager, PhilipZhu, JunZhang, BinSullivan, Patrick FChess, AndrewPurcell, Shaun MShinobu, Leslie AMangravite, Lara MToyoshiba, HiroyoshiGur, Raquel EHahn, Chang-GyuLewis, David AHaroutunian, VahramPeters, Mette ALipska, Barbara KBuxbaum, Joseph DSchadt, Eric EHirai, KeisukeRoeder, KathrynBrennand, Kristen JKatsanis, NicholasDomenici, EnricoDevlin, BernieSklar, Pamela2017-04-062016Fromer, M., P. Roussos, S. K. Sieberts, J. S. Johnson, D. H. Kavanagh, T. M. Perumal, D. M. Ruderfer, et al. 2016. “Gene Expression Elucidates Functional Impact of Polygenic Risk for Schizophrenia.” Nature neuroscience 19 (11): 1442-1453. doi:10.1038/nn.4399. http://dx.doi.org/10.1038/nn.4399.http://nrs.harvard.edu/urn-3:HUL.InstRepos:32071902Over 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 schizophrenia cases (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 changes neurodevelopment in zebrafish; knockdown of FURIN in human neural progenitor cells yields abnormal migration. Of 693 genes showing significant case/control differential expression, their fold changes are ≤ 1.33, and an independent cohort yields similar results. Gene co-expression implicates a network relevant for schizophrenia. Our findings show schizophrenia is polygenic and highlight the utility of this resource for mechanistic interpretations of genetic liability for brain diseases.en-USSchizophreniadorsolateral prefrontal cortexpostmortem studygene expressionRNA-seqcase-control studybiomarkereQTLfunctional GWASzebrafishhiPSCJournal Article2017-04-0610.1038/nn.4399