Observational studyNature neuroscience2021
Brain gene co-expression networks link complement signaling with convergent synaptic pathology in schizophrenia.
Observational study in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Meta-analytic evidence of elevated choline, reduced N-acetylaspartate, and normal creatine in schizophrenia and their moderation by measurement quality, echo time, and medication status.NeuroImage. Clinical · 2023Pooled it
- Perturbation of genes linked to common schizophrenia risk variants identifies cilia programs.bioRxiv : the preprint server for biology · 2026Article
- Neuroinflammation: an unfortunate term to describe schizophrenia.Molecular psychiatry · 2026Review
- Imaging Genomics Across Primate Species: Advancing Understanding of Neurological and Psychiatric Disorders.Neuroscience bulletin · 2026Review
- Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.Nature communications · 2026Article
- Immune involvement in neuropsychiatric disorders: Insights from single-cell transcriptomic studies.Psychiatry and clinical neurosciences · 2026Review
- Article
- Increase in Comforting Behavior (Allogrooming) During Social Interaction in Male Mice Deficient for theBrain sciences · 2026Article
- Polyunsaturated fatty acids and psychotic disorders: integrating mechanistic, genetic, and clinical evidence.Frontiers in nutrition · 2026Review
- Review
- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.International journal of molecular sciences · 2025Review
- Schizophrenia-associated changes in neuronal subpopulations in the human midbrain.Brain : a journal of neurology · 2025Article
- Tissue block-resolved developmental transcriptomic atlas of human fetal brainstem reveals gene modules with implications for neurological disorders.Frontiers in cell and developmental biology · 2025Article
- Neuronal Synaptic Communication and Mitochondrial Energetics in Human Health and Disease.Advances in experimental medicine and biology · 2025Review
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Schizophrenia genomics: genetic complexity and functional insights.Nature reviews. Neuroscience · 2024Review
- The Role of KDM2A and H3K36me2 Demethylation in Modulating MAPK Signaling During Neurodevelopment.Neuroscience bulletin · 2024Article
- Synaptic pruning in schizophrenia is not classical.Brain, behavior, and immunity · 2024Article
- Circuit-Wide Gene Network Analysis Reveals Sex-Specific Roles for Phosphodiesterase 1b in Cocaine Addiction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Article
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 1 institution in 1 country.
Funding
Abstract
The most significant common variant association for schizophrenia (SCZ) reflects increased expression of the complement component 4A (C4A). Yet, it remains unclear how C4A interacts with other SCZ risk genes or whether the complement system more broadly is implicated in SCZ pathogenesis. Here, we integrate several existing, large-scale genetic and transcriptomic datasets to interrogate the functional role of the complement system and C4A in the human brain. Unexpectedly, we find no significant genetic enrichment among known complement system genes for SCZ. Conversely, brain co-expression network analyses using C4A as a seed gene reveal that genes downregulated when C4A expression increases exhibit strong and specific genetic enrichment for SCZ risk. This convergent genomic signal reflects synaptic processes, is sexually dimorphic and most prominent in frontal cortical brain regions, and is accentuated by smoking. Overall, these results indicate that synaptic pathways-rather than the complement system-are the driving force conferring SCZ risk.
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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.