Bipolar Disorder Working Group Leadership

Arianna Di Florio, MD
Executive Team
Co-Director
Phenotype Group
Co-Chair
Data Access Committee Representative
Outreach Committee Liaison



Work with us!
If you have questions regarding the PGC BIP workgroup or projects that are currently being conducted, please contact the workgroup chairs.
For any questions or ideas related to research dissemination (e.g., via this webpage, social media, blogs, press outlets), please contact the workgroup outreach liaison.
If you have questions about how to access summary statistics or genotype-level data, or are interested to submit a secondary analysis proposal, please contact the workgroup data access committee representative.
About Us
Our History
The Bipolar Disorder workgroup has been a part of the PGC since the beginning of PGC. Our membership has grown to include investigators from more than 200 institutions world-wide.
Our members are clinical and basic science researchers with a wide range of expertise from psychiatry to psychology, human genetics, biostatistics, bioinformatics, cellular modelling and drug discovery.
Our Motivation
Bipolar disorder is a mental health condition that affects mood, energy levels, activity, and concentration or focus. The main symptoms of bipolar disorder are episodes of extreme highs, called mania, and lows (depression). These highs and lows are different from the ups and downs we all experience. They are often acute and can last for several weeks, causing significant distress and interfering with daily life. Episodes of illness can occur occasionally and at irregular intervals or be long-lasting. In many cases, bipolar disorder requires lifetime treatment, even when symptoms are not present.
The World Health Organisation ranks bipolar disorder as one of the top causes of lost years of life and health in 15 to 44 year olds (PMID: 23993280). Bipolar disorder can increase the risk of suicide by 10-30 times (PMID: 31344941) and yet it can take an average of 8 years (or more) to get a diagnosis. This is why the PGC BD working group is trying to identify regions of genetic code which may help us to understand and treat the condition.
Get Involved!
We are currently looking to increase the number of studies with genotype and clinical information on individuals with bipolar disorder, including those from overlooked ancestry groups. By linking genetic and clinical data, we hope to identify different sub-groups of individuals with bipolar disorder with different genetic signatures. Our analyses may provide useful information to develop new, more effective and tailored treatments and improve the management of bipolar disorder or of the risk of developing it.
We have monthly conference calls to discuss the management of the group and regular email contact on a list serve. For our open source commitment and data sharing policy, please read the PGC's MOU.
If you think you are able to contribute to our workgroup, please contact the chair, Ole Andreassen.
Major Accomplishments
Latest Results
The exact cause of bipolar disorder is unknown, but it is likely that there is no single cause. Instead, a combination of factors may contribute to the condition. This means genetic factors are not the sole determinant of bipolar disorder and environment does also play a role.
Research suggests that genetic factors are largely responsible for bipolar disorder running in families. They are believed to account for 60–80 percent of the risk of developing the disorder (PMID: 23663951). However, most people who have a close relative with bipolar disorder will not develop any psychiatric disorder and most people with bipolar disorder don’t have any family member affected.
To try and better understand this, our group recently conducted the largest genome-wide association study of bipolar disorder to date, comprising over 2.9 million participants, with more than 158,000 who experienced bipolar disorder (PMID: 39843750). We found 298 regions of the genome linked to increased risk for bipolar disorder, which mapped onto 36 genes. This work highlighted important brain regions and cell types such as GABAergic interneurons and medium spiny neurons in the prefrontal cortex and hippocampus but also cells within the intestine and pancreas. These findings may help us better understand the mechanisms and biology behind bipolar disorder.
Our group has also contributed to cross-disorder analyses that explored the genetic overlap with other major psychiatric disorders (PMID: 23933821, PMID: 23453885), including the identification of biological pathways shared by schizophrenia, major depression and bipolar disorder (PMID: 26007216). Together with the Schizophrenia working group, we have identified genetic regions that differentiate between the two disorders and examined the effect of schizophrenia genetic risk on the presentation of bipolar disorder and vice versa (PMID: 29906448).
Publications
O’Connell, K. S., Koromina, M., van der Veen, T., Boltz, T., David, F. S., Yang, J. M. K., ... & Sindermann, L. (2025). Genomics yields biological and phenotypic insights into bipolar disorder. Nature, 1-12.
https://doi.org/10.1038/s41586-024-08468-9
Mullins, N., Forstner, A. J., O’Connell, K. S., Coombes, B., Coleman, J. R., Qiao, Z., ... & Potash, J. B. (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature genetics, 53(6), 817-829.
https://doi.org/10.1038/s41588-021-00857-4
Stahl, E. A., Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., ... & Reif, A. (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature genetics, 51(5), 793-803.
https://doi.org/10.1038/s41588-019-0397-8
Coleman, J. R., Gaspar, H. A., Bryois, J., Byrne, E. M., Forstner, A. J., Holmans, P. A., ... & Lawson, W. B. (2020). The genetics of the mood disorder spectrum: genome-wide association analyses of more than 185,000 cases and 439,000 controls. Biological psychiatry, 88(2), 169-184.
https://doi.org/10.1016/j.biopsych.2019.10.015
Ruderfer, D. M., Ripke, S., McQuillin, A., Boocock, J., Stahl, E. A., Pavlides, J. M. W., ... & Freedman, R. (2018). Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell, 173(7), 1705-1715.