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000275859 0247_ $$2doi$$a10.1016/j.nsa.2024.104075
000275859 037__ $$aDZNE-2025-00094
000275859 1001_ $$aGarrett, Lillian$$b0
000275859 245__ $$aCo-expression of prepulse inhibition and Schizophrenia genes in the mouse and human brain
000275859 260__ $$aAmsterdam$$bElsevier$$c2024
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000275859 520__ $$aSchizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Accumulating rare and genome-wide association study (GWAS) common risk variant information has yet to yield robust mechanistic insight. Leveraging large-scale gene deletion mouse phenomic data thus has potential to functionally interrogate and prioritize human disease genes. To this end, we applied a cross-species network-based approach to parse an extensive mouse gene set (188 genes) associated with disrupted prepulse inhibition (PPI), a Schizophrenia endophenotype. Integrating PPI genes with high-resolution mouse and human brain transcriptomic data, we identified functional and disease coherent co-expression modules through hierarchical clustering and weighted gene co-expression network analysis (WGCNA). In two modules, Schizophrenia risk and mouse PPI genes converged based on telencephalic patterning. The associated neuronal genes were highly expressed in cingulate cortex and hippocampus; implicated in synaptic function and neurotransmission and overlapped with the greatest proportion of rare variants. Concordant neuroanatomical patterning revealed novel core Schizophrenia-relevant genes consistent with the Omnigenic hypothesis of complex traits. Among other genes discussed, the developmental and post-synaptic scaffold TANC2 (Tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2) emerged from both networks as a novel core genetic driver of Schizophrenia altering PPI. Aspects of psychiatric disease comorbidity and phenotypic heterogeneity are also explored. Overall, this study provides a framework and galvanizes the value of mouse preclinical genetics and PPI to prioritize both existing and novel human Schizophrenia candidate genes as druggable targets.
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000275859 7001_ $$0P:(DE-2719)9000367$$aTrumbach, Dietrich$$b1
000275859 7001_ $$aLee, Donghyung$$b2
000275859 7001_ $$00000-0002-4869-0974$$aMandillo, Silvia$$b3
000275859 7001_ $$00000-0001-5636-5314$$aSamaco, Rodney$$b4
000275859 7001_ $$aFlenniken, Ann M.$$b5
000275859 7001_ $$aStewart, Michelle$$b6
000275859 7001_ $$aAguilar-Pimental, Juan A.$$b7
000275859 7001_ $$aAmarie, Oana V.$$b8
000275859 7001_ $$aBecker, Lore$$b9
000275859 7001_ $$aCalzada-Wack, Julia$$b10
000275859 7001_ $$aDa Silva-Buttkus, Patricia$$b11
000275859 7001_ $$aDragano, Nathalia$$b12
000275859 7001_ $$aKraiger, Markus$$b13
000275859 7001_ $$aLengger, Christoph$$b14
000275859 7001_ $$aLeuchtenberger, Stefanie$$b15
000275859 7001_ $$aMarschall, Susan$$b16
000275859 7001_ $$aOestereicher, Manuela A.$$b17
000275859 7001_ $$aRathkolb, Birgit$$b18
000275859 7001_ $$aSanz-Moreno, Adrián$$b19
000275859 7001_ $$aSeisenberger, Claudia$$b20
000275859 7001_ $$aSpielmann, Nadine$$b21
000275859 7001_ $$aStoeger, Claudia$$b22
000275859 7001_ $$aKumar, Vivek$$b23
000275859 7001_ $$aKeskivali, Piia$$b24
000275859 7001_ $$aKing, Ruairidh$$b25
000275859 7001_ $$aHaselimashhadi, Hamed$$b26
000275859 7001_ $$aBezginov, Alexandr$$b27
000275859 7001_ $$aNorris, Clare$$b28
000275859 7001_ $$aTaylor, Sarah$$b29
000275859 7001_ $$aPimm, Dale$$b30
000275859 7001_ $$aKelsey, Lois$$b31
000275859 7001_ $$aBerberovic, Zorana$$b32
000275859 7001_ $$aQu, Dawei$$b33
000275859 7001_ $$aD'Souza, Abigail$$b34
000275859 7001_ $$aBradaschia, Vivian$$b35
000275859 7001_ $$aEskandarian, Mohammed$$b36
000275859 7001_ $$aShang, Xueyuan$$b37
000275859 7001_ $$aDuffin, Kyle$$b38
000275859 7001_ $$aRoberton, Kyle$$b39
000275859 7001_ $$aXu, Catherine$$b40
000275859 7001_ $$aBaguinat, Gloria$$b41
000275859 7001_ $$aLaurin, Valerie$$b42
000275859 7001_ $$aLan, Qing$$b43
000275859 7001_ $$aSleep, Gillian$$b44
000275859 7001_ $$aLintott, Lauri$$b45
000275859 7001_ $$aGertsenstein, Marina$$b46
000275859 7001_ $$aTondat, Sandra$$b47
000275859 7001_ $$aCruz, Maribelle$$b48
000275859 7001_ $$aMiller, David$$b49
000275859 7001_ $$aBezginov, Alexandr$$b50
000275859 7001_ $$aSorg, Tania$$b51
000275859 7001_ $$aRiet, Fabrice$$b52
000275859 7001_ $$aTolentino, Heather$$b53
000275859 7001_ $$aTolentino, Todd$$b54
000275859 7001_ $$aSchuchbauer, Mike$$b55
000275859 7001_ $$aHockenbury, Nichole$$b56
000275859 7001_ $$aBeeman, Karrie$$b57
000275859 7001_ $$aPedroia, Sheryl$$b58
000275859 7001_ $$aSalazar, Jason$$b59
000275859 7001_ $$aHeffner, Mollie$$b60
000275859 7001_ $$aHsu, Joanne$$b61
000275859 7001_ $$aFletcher, Colin$$b62
000275859 7001_ $$aVanzanten, Maya$$b63
000275859 7001_ $$aGolini, Elisabetta$$b64
000275859 7001_ $$aSeavitt, John R.$$b65
000275859 7001_ $$aLanza, Denise G.$$b66
000275859 7001_ $$aLorenzo, Isabel$$b67
000275859 7001_ $$aGaspero, Angelina$$b68
000275859 7001_ $$aRios, Amanda$$b69
000275859 7001_ $$aWhite, Jacqueline K.$$b70
000275859 7001_ $$aMcKerlie, Colin$$b71
000275859 7001_ $$00000-0001-9619-146X$$aNutter, Lauryl M. J.$$b72
000275859 7001_ $$aVukobradovic, Igor$$b73
000275859 7001_ $$aVeeraragavan, Surabi$$b74
000275859 7001_ $$aYuva, Lisa$$b75
000275859 7001_ $$aHeaney, Jason D.$$b76
000275859 7001_ $$aDickinson, Mary E.$$b77
000275859 7001_ $$00000-0002-4704-7055$$aMeziane, Hamid$$b78
000275859 7001_ $$00000-0001-7049-6900$$aHérault, Yann$$b79
000275859 7001_ $$00000-0002-0572-0600$$aWells, Sara$$b80
000275859 7001_ $$00000-0002-5318-4144$$aLloyd, K. C. Kent$$b81
000275859 7001_ $$aBower, Lynette$$b82
000275859 7001_ $$aLanoue, Louise$$b83
000275859 7001_ $$00000-0002-3315-7333$$aClary, Dave$$b84
000275859 7001_ $$00000-0003-2078-6779$$aZimprich, Annemarie$$b85
000275859 7001_ $$aGailus-Durner, Valerie$$b86
000275859 7001_ $$aFuchs, Helmut$$b87
000275859 7001_ $$aBrown, Steve D. M.$$b88
000275859 7001_ $$00000-0002-5642-5062$$aChesler, Elissa J.$$b89
000275859 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b90$$udzne
000275859 7001_ $$aHrabě de Angelis, Martin$$b91
000275859 7001_ $$aHölter, Sabine M.$$b92
000275859 773__ $$0PERI:(DE-600)3154568-3$$a10.1016/j.nsa.2024.104075$$gVol. 3, p. 104075 -$$p104075$$tNeuroscience Applied$$v3$$x2772-4085$$y2024
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