ArticleGenome biology2023
Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- A decade of discovery: Leveraging genomic data in the ABCD study to illuminate adolescent neurodevelopment.Developmental cognitive neuroscience · 2026Review
- Polygenic score for C-reactive protein is linked to faster cortical thinning and psychopathology risk in adolescents.Nature. Mental health · 2026Article
- Genetics and Phenotypes of Late-Onset Neurodegeneration in Neurodevelopmental Disorders.Cureus · 2025Review
- Serum proteomic correlates of mental health symptoms in a representative UK population sample.Brain, behavior, & immunity - health · 2025Article
- Association of Polygenic Risk Scores for Schizophrenia with Psychosis-Proneness Indicators in the General Population: A Narrative Review.Consortium psychiatricum · 2025Review
- Attention-mediated genetic influences on psychotic symptomatology in adolescence.Nature. Mental health · 2024Article
- Quality over quantity: powering neuroimaging samples in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Mapping the genetic and phenotypic landscape of neonatal C3 and C4 protein concentrations.Cell genomics · 2023Article
- The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders.Cell genomics · 2023Article
- Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naïve patients with first-episode schizophrenia.Schizophrenia (Heidelberg, Germany) · 2023Article
- Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.Genome biology · 2023Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundIncreased expression of the complement component 4A (C4A) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9-12 years to examine the relationship between genetically regulated expression (GREx) of C4A, childhood brain structure, cognition, and psychiatric symptoms.
resultsWhile C4A GREx is not related to childhood psychotic experiences, cognition, or global measures of brain structure, it is associated with a localized reduction in regional surface area (SA) of the entorhinal cortex. Furthermore, we show that reduced entorhinal cortex SA at 9-10 years predicts a greater number and severity of psychosis-like events at 1-year and 2-year follow-up time points. We also demonstrate that the effects of C4A on the entorhinal cortex are independent of genome-wide polygenic risk for schizophrenia.
conclusionsOur results suggest neurodevelopmental effects of C4A on childhood medial temporal lobe structure, which may serve as a biomarker for schizophrenia risk prior to symptom onset.
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Registered trials
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