Good news! What a massive effort to come up with this result!
"... Bipolar disorder is a severe, heritable mood disorder that affects approximately 1 percent of the population and often begins in early adulthood. ..."
"The main treatment for bipolar disorder, lithium, was approved a half-century ago but doesn't help all patients and has significant side effects. Little progress has been made in finding better therapies, in part because scientists don’t fully understand how the condition arises or exactly how lithium improves symptoms when it does work.
A genetic study involving thousands of people with bipolar disorder has revealed new insight into the condition’s molecular underpinnings. ... the effort pinpoints a gene called AKAP11 as a strong risk factor for both bipolar disorder and schizophrenia. The findings may provide clues to how lithium works, as the AKAP-11 protein is known to interact with a molecular pathway modified by the drug. While many common genetic variants of small effects have been discovered, AKAP11 is the first gene found to have a large effect on bipolar disorder risk. ..."
From the 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."
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