A landmark study isolates the genetic architecture of mania for the first time, identifying 71 variants and pointing toward earlier diagnosis and targeted treatment.
Researchers at King’s College London and the University of Florence have identified the specific genetic blueprint of mania in bipolar disorder. The findings, published in the journal Biological Psychiatry in January 2026, mark the first time scientists have isolated the genetic architecture of mania from the broader genetic signals of bipolar disorder.
The study analyzed genetic data from more than 600,000 people, including over 27,000 diagnosed with severe bipolar disorder and over 576,000 studied for depression. Using an advanced statistical method that subtracts the genetic effects associated with depression from those seen in bipolar disorder, the team isolated the genetic component that is specific to mania.
The results were striking. Mania accounts for more than 80 percent of the genetic variation in bipolar disorder, confirming what clinicians have long suspected. Mania is not just one symptom of the condition. It is the core.
The researchers identified 71 genetic variants linked specifically to mania, including 18 regions of genes that had never been associated with bipolar disorder before. Many of these newly identified genes are involved in voltage-gated calcium channels, which play a critical role in communication between brain cells and in regulating mood.
“By isolating the genetic architecture of mania, we have taken a crucial step towards understanding the core biology of bipolar disorder,” said Dr. Giuseppe Pierpaolo Merola, an MRC Clinical Research Training Fellow at King’s College London and lead author of the study. “This allows us to see what makes mania distinct, rather than viewing bipolar disorder simply as a mixture of mania, depression and psychosis.”
When compared genetically with other traits, mania showed a distinct profile. It shared less genetic overlap with substance use and more with measures related to wellbeing and educational attainment than bipolar disorder as a whole. That distinction suggests mania may be driven by different biological pathways than previously understood.
Why It Matters for Diagnosis
Bipolar disorder affects roughly 2 percent of people worldwide, but reaching the correct diagnosis takes an average of nearly a decade. Many people first seek help during depressive episodes, when the condition can look very similar to major depression or schizophrenia. Patients often cycle through multiple incorrect diagnoses before bipolar disorder is correctly identified.
By defining the genetic features unique to mania, this research moves the field closer to identifying early biological indicators that could shorten that diagnostic journey.
“Mania is what defines bipolar disorder, yet it has remained surprisingly difficult to study in its own right,” said Professor Gerome Breen, Professor of Psychiatric Genetics at King’s College London and senior author of the study. “In the longer term, this could help clinicians recognise bipolar disorder earlier, reduce the long delays many patients face before receiving a diagnosis, and improve outcomes through more targeted treatment.”
Treatment Implications
The findings also point toward potential treatment pathways. The prominence of calcium channel genes among the 71 variants suggests that medications targeting these systems, including established drugs like lithium, may work through these specific biological mechanisms. Understanding that connection could help researchers develop more targeted therapies with fewer side effects.
The research was funded by the National Institute for Health and Care Research Maudsley Biomedical Research Centre.
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