ArticleNature communications2023
Human forebrain organoid-based multi-omics analyses of PCCB as a schizophrenia associated gene linked to GABAergic pathways.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 4 of them syntheses that pooled it.
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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.
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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.
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Who cites it
27 citing papers in PubMed, 4 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Multiancestry and Multitrait GWAS Meta-Analysis on Schizophrenia With a Sample of 322,321 Unveils Genetic Links to Chronic Lung Diseases.Genes, brain, and behavior · 2026Pooled it
- Multi-Trait Genetic Insights Into Schizophrenia Across Ancestries: Genome-Wide Association Meta-Analyses, Machine Learning, and Drug Repurposing Study.Brain and behavior · 2026Pooled it
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-Analyses of Brain and Blood Samples and iPSC-Derived Organoids.Alpha psychiatry · 2026Pooled it
- Astrocytic connexin 43 hemichannel dysregulation drives prefrontal circuit dysfunction and schizophrenia-like behaviors.Molecular psychiatry · 2026Article
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Dysregulation of the BRD2-FGF17 Signal Pathway Induces Abnormal Forebrain Development Associated with Schizophrenia.Neuroscience bulletin · 2026Article
- Functional variants at 1p36.23 confer risk of schizophrenia through modulating RERE.Nature communications · 2026Article
- Advances in the pathophysiological study of brain development: application of cerebral organoid combined with Spatial omics technology.Stem cell research & therapy · 2026Review
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- Pluripotent stem cells-based neural organoids for modelling human brain development and diseases.Cell & bioscience · 2025Review
- Transcriptomic Analysis of the Human Habenula in Schizophrenia.The American journal of psychiatry · 2025Article
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- Bioelectronic Interfaces and Sensors for Neural Organoids.Microsystems & nanoengineering · 2025Review
- Analysis of biased allelic enhancer activity of schizophrenia-linked common variants.Communications biology · 2025Article
- The ADCY1-mediated cAMP signaling pathway mediates functional effects of montelukast treatment in brain organoids.Cellular and molecular life sciences : CMLS · 2025Article
- Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025Review
- Protein Arginine Methyltransferases from Regulatory Function to Clinical Implication in Central Nervous System.Cellular and molecular neurobiology · 2025Review
- The genetic overlap and causal relationship between attention deficit hyperactivity disorder and obstructive sleep apnea: a large-scale genomewide cross-trait analysis.BMC psychiatry · 2025Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Identifying genes whose expression is associated with schizophrenia (SCZ) risk by transcriptome-wide association studies (TWAS) facilitates downstream experimental studies. Here, we integrated multiple published datasets of TWAS, gene coexpression, and differential gene expression analysis to prioritize SCZ candidate genes for functional study. Convergent evidence prioritized Propionyl-CoA Carboxylase Subunit Beta (PCCB), a nuclear-encoded mitochondrial gene, as an SCZ risk gene. However, the PCCB's contribution to SCZ risk has not been investigated before. Using dual luciferase reporter assay, we identified that SCZ-associated SNPs rs6791142 and rs35874192, two eQTL SNPs for PCCB, showed differential allelic effects on transcriptional activities. PCCB knockdown in human forebrain organoids (hFOs) followed by RNA sequencing analysis revealed dysregulation of genes enriched with multiple neuronal functions including gamma-aminobutyric acid (GABA)-ergic synapse. The metabolomic and mitochondrial function analyses confirmed the decreased GABA levels resulted from inhibited tricarboxylic acid cycle in PCCB knockdown hFOs. Multielectrode array recording analysis showed that PCCB knockdown in hFOs resulted into SCZ-related phenotypes including hyper-neuroactivities and decreased synchronization of neural network. In summary, this study utilized hFOs-based multi-omics analyses and revealed that PCCB downregulation may contribute to SCZ risk through regulating GABAergic pathways, highlighting the mitochondrial function in SCZ.
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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 Socratic graph.