NIH-funded study of people with diverse ancestries revealed new genes involved in the disorder and different genes contributing to specific disorder subtypes
• Research Highlight
Bipolar disorder involves fluctuating periods of manic episodes (marked by extremely “up” or irritable moods) and depressive episodes (marked by very “down” moods or lack of pleasure). Although effective treatments are available, symptoms often return over time, and maintaining long-term treatment can be challenging. Evidence suggests a person’s risk for developing bipolar disorder is influenced by many genes, but open questions remain about the full range of genes involved and whether they differ for specific subtypes.
What did the researchers do in the study?
The largest genome-wide study of people with bipolar disorder sheds new light on the genetic architecture and biological mechanisms involved in this common and often disabling mental illness. The findings from the study, funded by the National Institute of Health, may pave the way for more targeted and personalized treatments that could improve the lives of people with bipolar disorder.
The worldwide collaborative study was led by researchers in the Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. The study included 158,036 people living with bipolar disorder and 2,796,499 people without the disorder across 79 clinical, community, and self-report cohorts—making it the largest such study to date. The participants were of European, East Asian, African American, and Latino ancestries, in contrast to previous studies conducted almost exclusively with people of European ancestry.
What did the results show?
The results revealed an over four-fold increase in the number of genes associated with bipolar disorder, identifying nearly 300 gene locations and 36 unique genes most likely to be linked to the disorder. Many of these genes overlapped with those previously implicated in the risk for other mental disorders such as schizophrenia and depression.
The researchers also identified differences in the genetic architecture across bipolar disorder subtypes. The findings suggest that genetics play a key role across a broad spectrum of conditions that fall under the umbrella of bipolar disorder. These range from less common but more severe conditions that lead people to seek psychiatric care to conditions that are less disabling but more common.
The next big challenge for the field is to understand why bipolar disorder varies so much from person to person and the degree to which genetic factors can explain individual variation.
Reference
O’Connell, K. S., Koromina, M., van der Veen, T., Boltz, T., David, F. S., Yang, J. M. K., Lin, K.-H., Wang, X., Coleman, J. R. I., Mitchell, B. L., McGrouther, C. C., Rangan, A. V., Lind, P. A., Koch, E., Harder, A., Parker, N., Bendl, J., Adorjan, K., Agerbo, E. … Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. (2025). Genomics yields biological and phenotypic insights into bipolar disorder. Nature. https://doi.org/10.1038/s41586-024-08468-9