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@ARTICLE{Garrett:275859,
      author       = {Garrett, Lillian and Trumbach, Dietrich and Lee, Donghyung
                      and Mandillo, Silvia and Samaco, Rodney and Flenniken, Ann
                      M. and Stewart, Michelle and Aguilar-Pimental, Juan A. and
                      Amarie, Oana V. and Becker, Lore and Calzada-Wack, Julia and
                      Da Silva-Buttkus, Patricia and Dragano, Nathalia and
                      Kraiger, Markus and Lengger, Christoph and Leuchtenberger,
                      Stefanie and Marschall, Susan and Oestereicher, Manuela A.
                      and Rathkolb, Birgit and Sanz-Moreno, Adrián and
                      Seisenberger, Claudia and Spielmann, Nadine and Stoeger,
                      Claudia and Kumar, Vivek and Keskivali, Piia and King,
                      Ruairidh and Haselimashhadi, Hamed and Bezginov, Alexandr
                      and Norris, Clare and Taylor, Sarah and Pimm, Dale and
                      Kelsey, Lois and Berberovic, Zorana and Qu, Dawei and
                      D'Souza, Abigail and Bradaschia, Vivian and Eskandarian,
                      Mohammed and Shang, Xueyuan and Duffin, Kyle and Roberton,
                      Kyle and Xu, Catherine and Baguinat, Gloria and Laurin,
                      Valerie and Lan, Qing and Sleep, Gillian and Lintott, Lauri
                      and Gertsenstein, Marina and Tondat, Sandra and Cruz,
                      Maribelle and Miller, David and Bezginov, Alexandr and Sorg,
                      Tania and Riet, Fabrice and Tolentino, Heather and
                      Tolentino, Todd and Schuchbauer, Mike and Hockenbury,
                      Nichole and Beeman, Karrie and Pedroia, Sheryl and Salazar,
                      Jason and Heffner, Mollie and Hsu, Joanne and Fletcher,
                      Colin and Vanzanten, Maya and Golini, Elisabetta and
                      Seavitt, John R. and Lanza, Denise G. and Lorenzo, Isabel
                      and Gaspero, Angelina and Rios, Amanda and White, Jacqueline
                      K. and McKerlie, Colin and Nutter, Lauryl M. J. and
                      Vukobradovic, Igor and Veeraragavan, Surabi and Yuva, Lisa
                      and Heaney, Jason D. and Dickinson, Mary E. and Meziane,
                      Hamid and Hérault, Yann and Wells, Sara and Lloyd, K. C.
                      Kent and Bower, Lynette and Lanoue, Louise and Clary, Dave
                      and Zimprich, Annemarie and Gailus-Durner, Valerie and
                      Fuchs, Helmut and Brown, Steve D. M. and Chesler, Elissa J.
                      and Wurst, Wolfgang and Hrabě de Angelis, Martin and
                      Hölter, Sabine M.},
      title        = {{C}o-expression of prepulse inhibition and {S}chizophrenia
                      genes in the mouse and human brain},
      journal      = {Neuroscience Applied},
      volume       = {3},
      issn         = {2772-4085},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00094},
      pages        = {104075},
      year         = {2024},
      abstract     = {Schizophrenia 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.},
      cin          = {AG Wurst},
      cid          = {I:(DE-2719)1140001},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.1016/j.nsa.2024.104075},
      url          = {https://pub.dzne.de/record/275859},
}