PuSH - Publication Server of Helmholtz Zentrum München: Co-expression of prepulse inhibition and Schizophrenia genes in the mouse and human brain.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Garrett, L. ; Trümbach, D. ; Lee, D.* ; Mandillo, S.* ; Samaco, R.C.* ; Flenniken, A.M.* ; Stewart, M.* ; White, J.K.* ; McKerlie, C.* ; Nutter, L.M.J.* ; Vukobradovic, I.* ; Veeraragavan, S.* ; Yuva, L.* ; Heaney, J.D.* ; Dickinson, M.E.* ; Meziane, H.* ; Hérault, Y.* ; Wells, S.* ; Lloyd, K.C.K.* ; Bower, L.* ; Lanoue, L.* ; Clary, D.* ; Zimprich, A. ; Gailus-Durner, V. ; Fuchs, H. ; Brown, S.D.M.* ; Chesler, E.J.* ; Wurst, W. ; Hrabě de Angelis, M. ; Hölter, S.M.

Co-expression of prepulse inhibition and Schizophrenia genes in the mouse and human brain.

Neurosci. App. 3:104075 (2024)

Publ. Version/Full Text

DOI

	Open Access Hybrid

Abstract
Metrics
Extra information

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. As-pects 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.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Altmetric

0.000