Bipolar patients display stoichiometric imbalance of gene expression in post-mortem brain samples.
Mol Psychiatry
; 29(4): 1128-1138, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38351171
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trastorno Bipolar
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Encéfalo
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Estudio de Asociación del Genoma Completo
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Mol Psychiatry
Asunto de la revista:
BIOLOGIA MOLECULAR
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PSIQUIATRIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Noruega