Analysis of gene co-expression connectivity dynamics implicates aberrant neuron-oligodendroglia interactions in schizophrenia

=349; sex: M/F = 242/107). Here we identify differentially connected genes (DCG) in schizophrenia networks that deviate from architectural relationships characteristic of neurotypical gene networks based on three network metrics- total connectivity (kTot), clustering coefficient (C), and intra-module degree (kIn). We find multiple DCG consistent across all brain regions, most of which we then independently confirm in brain single nuclei (snRNAseq) data and in four independent human iPSC-derived brain organoids. DCG specific for each network parameter shows enrichment in schizophrenia genetic signal, in pathways prominently related to neurons and oligodendroglia functionality, and in cell-type specific co-expression patterns that differ between neurotypical and schizophrenia, implicating neuronal-oligodendroglia incoordination.

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Publication Details

Journal
Nature Communications
Published
2026-07-16
DOI
https://doi.org/10.1038/s41467-026-75470-2
Primary Topic
Genetic Associations and Epidemiology
Type
article
Field-Weighted Citation Impact
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article

Analysis of gene co-expression connectivity dynamics implicates aberrant neuron-oligodendroglia interactions in schizophrenia

Shizhong Han, Joel E. Kleinman, Tomoyo Sawada, Petra E. Vértes et al.
Nature Communications
Genetic Associations and Epidemiology
article

Analysis of gene co-expression connectivity dynamics implicates aberrant neuron-oligodendroglia interactions in schizophrenia

Shizhong Han, Joel E. Kleinman, Tomoyo Sawada, Petra E. Vértes, Jennifer A. Erwin, Edward Thomas Bullmore, Daniel R. Weinberger, Thomas M. Hyde, Eugenia Radulescu, Apuã C. M. Paquola
article en

Abstract

=349; sex: M/F = 242/107). Here we identify differentially connected genes (DCG) in schizophrenia networks that deviate from architectural relationships characteristic of neurotypical gene networks based on three network metrics- total connectivity (kTot), clustering coefficient (C), and intra-module degree (kIn). We find multiple DCG consistent across all brain regions, most of which we then independently confirm in brain single nuclei (snRNAseq) data and in four independent human iPSC-derived brain organoids. DCG specific for each network parameter shows enrichment in schizophrenia genetic signal, in pathways prominently related to neurons and oligodendroglia functionality, and in cell-type specific co-expression patterns that differ between neurotypical and schizophrenia, implicating neuronal-oligodendroglia incoordination.

Nature Communications
Institute of Physics (GB), Alzheimer's Association (US), Johns Hopkins University (US), University of Cambridge (GB), Johns Hopkins Medicine (US), Behavioral Pharma (United States) (US), Universidad San Carlos (PY), Lieber Institute for Brain Development (US)
Zero hunger
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Genetic Associations and Epidemiology
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