ArticleNature2016
Schizophrenia risk from complex variation of complement component 4.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04038840 (Imaging Synapses With [11C] UCB-J in the Human Brain), which is not on this map. Cited by 1,305 papers, 4 of them syntheses 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.
Imaging Synapses With [11C] UCB-J in the Human Brain
Who cites it
1,305 citing papers in PubMed, 4 syntheses or guidelines pooled it, 2,453 citations in OpenAlex.
- Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications.Molecular psychiatry · 2026Pooled it
- Genome-wide association studies of infant and toddler temperament in European and multi-ancestry populations.Nature human behaviour · 2026Pooled it
- Inflammatory cytokine alterations in genetic and clinical high risk groups of psychosis: a systematic review and network meta-analysis.Psychological medicine · 2026Pooled it
- Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.Arthritis & rheumatology (Hoboken, N.J.) · 2025Pooled it
- Neuropsychiatry genetics in Africa.Nature communications · 2026Review
- Sparse neuronal C4 elevation induces network-wide transcriptomic and lipid-droplet remodeling in the cortical microenvironment.PLoS computational biology · 2026Article
- A founder population reveals genetic variation with major effect on serious mental illness.medRxiv : the preprint server for health sciences · 2026Article
- Concomitant pathologies and their impact on schizophrenia: a narrative overview of current evidence.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Estimating protein isoform abundances with [Formula: see text].Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mismatch negativity matures in adolescence and without sensitivity to microglial depletion.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Complement component C4 regulates amyloid pathology and glial reactivity in mouse model of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Schizophrenia: Converging Neurobiological Mechanisms and Emerging Therapeutic Strategies.Biomolecules · 2026Review
- Review
- Advances in Complement Research: from Pathophysiology to Precision Medicine.Physiology (Bethesda, Md.) · 2026Review
- Retinal Origins of Aberrant Salience in Schizophrenia: The Perceptual Theory.Biological psychiatry global open science · 2026Review
- Schizophrenia Spectrum Biomarkers Consortium: Establishment of a Biorepository for the Discovery of Quantitative Fluid Biomarkers.Schizophrenia bulletin · 2026Article
- Article
- Global perspectives on central nervous system drug innovation: achievements, barriers, and priorities for the next decade.The international journal of neuropsychopharmacology · 2026Review
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
1,245 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
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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 OpenQuestion graph.