Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia.
Nat Genet
; 54(5): 541-547, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35410376
ABSTRACT
We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Transtorno Bipolar
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article