Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
Nature Genetics, ISSN: 1546-1718, Vol: 54, Issue: 5, Page: 541-547
2022
- 88Citations
- 175Captures
- 70Mentions
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- Citations88
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- CrossRef88
- 73
- Captures175
- Readers175
- 175
- Mentions70
- News Mentions68
- 68
- Blog Mentions2
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Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia
According to articles speculating, "results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 individuals diagnosed with bipolar disorder (BD), matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in BD patients among genes under strong evolutionary constraint, a signal evident in both major BD subtypes, bipolar 1
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Article Description
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). 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.
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Springer Science and Business Media LLC
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