ArticleMolecular psychiatry2024
Bipolar patients display stoichiometric imbalance of gene expression in post-mortem brain samples.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- Surveying alternative transcripts of disease-associated genes and their cell type specificity - a case study with ANK3.Translational psychiatry · 2026Article
- Evaluation of GABAergic and Glutamatergic Levels in the Dorsal Anterior Cingulate Cortex of Patients With Bipolar Disorder: A Cross-SectionalNeuropsychopharmacology reports · 2026Article
- New Genomics Discoveries Across the Bipolar Disorder Spectrum Implicate Neurobiological and Developmental Pathways.Biological psychiatry · 2025Review
- Transcription-Driven Repurposing of Cardiotonic Steroids for Lithium Treatment of Severe Depression.Cells · 2025Article
- Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder.International journal of molecular sciences · 2024Article
- Codes between Poles: Linking Transcriptomic Insights into the Neurobiology of Bipolar Disorder.Biology · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Bipolar disorder is a severe neuro-psychiatric condition where genome-wide association and sequencing studies have pointed to dysregulated gene expression as likely to be causal. We observed strong correlation in expression between GWAS-associated genes and hypothesised that healthy function depends on balance in the relative expression levels of the associated genes and that patients display stoichiometric imbalance. We developed a method for quantifying stoichiometric imbalance and used this to predict each sample's diagnosis probability in four cortical brain RNAseq datasets. The percentage of phenotypic variance on the liability-scale explained by these probabilities ranged from 10.0 to 17.4% (AUC: 69.4-76.4%) which is a multiple of the classification performance achieved using absolute expression levels or GWAS-based polygenic risk scores. Most patients display stoichiometric imbalance in three to ten genes, suggesting that dysregulation of only a small fraction of associated genes can trigger the disorder, with the identity of these genes varying between individuals.
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