Imagine constantly oscillating between feeling on top of the world and extremely low. Some days, you are impulsive with overflowing energy, while on other days, you are deeply depressed, lethargic, and devoid of energy.
Such abnormal mood swings are common for individuals with bipolar disorder.
The condition is largely genetic, meaning there is a congenital vulnerability to developing the disorder later in life.
"Bipolar disorder is one of the most heritable psychiatric disorders. Heritability is estimated to be around 80 percent, which is very high," says researcher Kevin O’Connell from the Centre for Precision Psychiatry at the University of Oslo.
"And yet, most of the underlying genes that increase the risk of the illness remain unknown," adds Professor and Centre leader Ole Andreassen, lead investigator of the study.
The most extensive study on bipolar disorder and genetics to date
Together with a large international research consortium, O’Connell and Andreassen conducted the most extensive study on bipolar disorder and genetics to date, involving over 2.9 million people. The findings were published in the prestigious journal Nature.
The researchers identified 298 genomic regions associated with bipolar disorder.
The study’s large scale and participant count increased the number of identified genomic regions nearly fourfold.
"267 of the 298 regions we found had not previously been linked to bipolar disorder," notes O’Connell.
The researchers further pinpointed 36 genes that play a crucial role in the condition's development.
More knowledge paves the way for better treatment
These results offer new insights into the biological mechanisms underlying the disease.
"By understanding the genetics behind the illness, we can use this knowledge to benefit patients," Andreassen says, and continues:
"This could lead to improved diagnosis and treatment options, early interventions, and preventive measures for individuals at risk of developing bipolar disorder".
Identified specific genetic regions
But what does it mean to have identified numerous genomic areas linked to bipolar disorder?
The genome is the complete set of genetic material in an organism, with DNA being the material carrying genetic information.
Discovering 298 genomic regions associated with bipolar disorder means that specific locations in our DNA sequence are connected to the disease.
Identifying such regions is crucial for understanding the genetic factors contributing to the disorder.
Neurons in specific brain regions might play significant roles
Within identified genomic regions, researchers can locate genes linked to a condition, which might influence disease risk and severity.
In this study, O’Connell and colleagues identified 36 key genes involved in bipolar disorder.
Although everyone is genetically unique, genetic information is shared with close relatives and provides clues about a disease's heritability.
Further analysis suggested that neurons in specific brain regions, like the prefrontal cortex and hippocampus, might play significant roles in bipolar disorder's development.
"More research is needed to understand this biology further," O’Connell says.
Are there differences in genetic risk between different types of bipolar disorder?
The study also indicates potential differences in genetic risk between bipolar disorder types 1 and 2, suggesting a spectrum of risk ranging from milder to more severe forms of the disorder.
"Understanding these genetic differences can help tailor more personalized treatment methods," Andreassen explains.
A wider impact
There are approximately 160,000 individuals living with bipolar disorder in Norway, and globally, around 40 to 50 million people are affected.
Bipolar disorder is linked to many negative outcomes, including suicide, and it takes an average of eight years to receive a diagnosis.
The researchers aimed to gain insights into genetic factors that increase the risk of bipolar disorder.
"Understanding the biological risk factors can also support clinicians in their decision making around managing the condition more effectively, offering more targeted treatments. Treatment can be tailored to the individual patient’s genetic profile and expected responses and side effects to treatment, " Andreassen says.
“While the findings may not immediately transform treatment, they offer long-term possibilities, including developing new medications targeting bipolar disorder's genetic factors”, he adds.
An international collaboration made it possible
An international research team, The Psychiatric Genomics Consortium, dedicated to exploring the genetic foundations of psychiatric disorders, conducted the world's largest study on the genetics of bipolar disorder to date.
Over 158,000 individuals with bipolar disorder and about 2.8 million healthy individuals participated, with data analyzed from people of European, East Asian, African American, and Latin American descent.
"Our team spans psychiatry, psychology, genetics, biostatistics, cell model development, and drug discovery exploration," explains O’Connell.
"This work was possible due to outstanding collaboration across the group," he concludes.
Reference
O’Connell, K. S., Koromina,?M., Van der Veen, T.,?Boltz, T.? David, F. S., et al. 2025. Genomics yields biological and phenotypic insights into bipolar disorder. Nature.?https://www.nature.com/articles/s41586-024-08468-9?