Bipolar patients display stoichiometric imbalance of gene expression in post-mortem brain samples.
Mol Psychiatry
; 29(4): 1128-1138, 2024 Apr.
Article
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Bipolar
/
Encéfalo
/
Estudo de Associação Genômica Ampla
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Psychiatry
Assunto da revista:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Noruega