Consensus molecular environment of schizophrenia risk genes in coexpression networks shifting across age and brain regions

Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus,...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2023-04, Vol.9 (15), p.eade2812
Main Authors: Pergola, Giulio, Parihar, Madhur, Sportelli, Leonardo, Bharadwaj, Rahul, Borcuk, Christopher, Radulescu, Eugenia, Bellantuono, Loredana, Blasi, Giuseppe, Chen, Qiang, Kleinman, Joel E, Wang, Yanhong, Sripathy, Srinidhi Rao, Maher, Brady J, Monaco, Alfonso, Rossi, Fabiana, Shin, Joo Heon, Hyde, Thomas M, Bertolino, Alessandro, Weinberger, Daniel R
Format: Article
Language:English
Subjects:
Brain
Caudate Nucleus
Human Genetics
Humans
Neuroscience
Prefrontal Cortex
Schizophrenia - genetics
SciAdv r-articles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Schizophrenia is a neurodevelopmental brain disorder whose genetic risk is associated with shifting clinical phenomena across the life span. We investigated the convergence of putative schizophrenia risk genes in brain coexpression networks in postmortem human prefrontal cortex (DLPFC), hippocampus, caudate nucleus, and dentate gyrus granule cells, parsed by specific age periods (total  = 833). The results support an early prefrontal involvement in the biology underlying schizophrenia and reveal a dynamic interplay of regions in which age parsing explains more variance in schizophrenia risk compared to lumping all age periods together. Across multiple data sources and publications, we identify 28 genes that are the most consistently found partners in modules enriched for schizophrenia risk genes in DLPFC; twenty-three are previously unidentified associations with schizophrenia. In iPSC-derived neurons, the relationship of these genes with schizophrenia risk genes is maintained. The genetic architecture of schizophrenia is embedded in shifting coexpression patterns across brain regions and time, potentially underwriting its shifting clinical presentation.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.ade2812