ArticleMolecular psychiatry2021
Combined cellomics and proteomics analysis reveals shared neuronal morphology and molecular pathway phenotypes for multiple schizophrenia risk genes.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- A Systematic Review of the Human Accelerated Regions in Schizophrenia and Related Disorders: Where the Evolutionary and Neurodevelopmental Hypotheses Converge.International journal of molecular sciences · 2023Pooled it
- Is it possible to prevent excessive synaptic pruning in schizophrenia? Possibilities and limitations.Frontiers in synaptic neuroscience · 2025Review
- Discovering functional interactions among schizophrenia-risk genes by combining behavioral genetics with cell biology.Neuroscience and biobehavioral reviews · 2024Review
- The omics era: a nexus of untapped potential for Mendelian chromatinopathies.Human genetics · 2024Review
- Treatability of the KMT2-Associated Neurodevelopmental Disorders Using Antisense Oligonucleotide-Based Treatments.Human mutation · 2024Review
- FEZ1 participates in human embryonic brain development by modulating neuronal progenitor subpopulation specification and migrations.iScience · 2023Article
- Cell-Type-Specific Neuroproteomics of Synapses.Biomolecules · 2023Review
- Intraneuronal tau aggregation induces the integrated stress response in astrocytes.Journal of molecular cell biology · 2023Article
- Aβ42 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer's disease brain extracts.Alzheimer's research & therapy · 2022Article
- Article
- Neuron-specific translational control shift ensures proteostatic resilience during ER stress.The EMBO journal · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models.International journal of molecular sciences · 2021Article
- Molecular Evolution of DNA Topoisomerase III Beta (TOP3B) in Metazoa.Journal of molecular evolution · 2021Article
- Article
- Neuroproteomics of the Synapse: Subcellular Quantification of Protein Networks and Signaling Dynamics.Molecular & cellular proteomics : MCP · 2021Review
- Advances in Proteomics Allow Insights Into Neuronal Proteomes.Frontiers in molecular neuroscience · 2021Review
- The many lives of type IA topoisomerases.The Journal of biological chemistry · 2020Review
- Recent Developments in Data Independent Acquisition (DIA) Mass Spectrometry: Application of Quantitative Analysis of the Brain Proteome.Frontiers in molecular neuroscience · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An enigma in studies of neuropsychiatric disorders is how to translate polygenic risk into disease biology. For schizophrenia, where > 145 significant GWAS loci have been identified and only a few genes directly implicated, addressing this issue is a particular challenge. We used a combined cellomics and proteomics approach to show that polygenic risk can be disentangled by searching for shared neuronal morphology and cellular pathway phenotypes of candidate schizophrenia risk genes. We first performed an automated high-content cellular screen to characterize neuronal morphology phenotypes of 41 candidate schizophrenia risk genes. The transcription factors Tcf4 and Tbr1 and the RNA topoisomerase Top3b shared a neuronal phenotype marked by an early and progressive reduction in synapse numbers upon knockdown in mouse primary neuronal cultures. Proteomics analysis subsequently showed that these three genes converge onto the syntaxin-mediated neurotransmitter release pathway, which was previously implicated in schizophrenia, but for which genetic evidence was weak. We show that dysregulation of multiple proteins in this pathway may be due to the combined effects of schizophrenia risk genes Tcf4, Tbr1, and Top3b. Together, our data provide new biological functions for schizophrenia risk genes and support the idea that polygenic risk is the result of multiple small impacts on common neuronal signaling pathways.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.