An international team of researchers has conducted the largest genome-wide association study (GWAS) of bipolar disorder to date, uncovering 298 regions of the genome associated with increased risk for the condition—a fourfold increase over previous studies. Published in Nature, the researchers analyzed data from 2.9 million individuals of diverse ancestries, including European, East Asian, African American, and Latino populations, shedding light on the complex genetic architecture of bipolar disorder.
Bipolar disorder, which affects an estimated 40–50 million people globally, is a lifelong mood disorder marked by episodes of mania and depression (bipolar I) or hypomania and depression (bipolar II). Despite its prevalence, the underlying biology of the condition remains elusive, and diagnosis often takes an average of eight years. By identifying DNA variations linked to the disorder, researchers hope to pave the way for improved treatments, earlier interventions, and precision medicine approaches.
The study, led by the Psychiatric Genomics Consortium, scanned over 6.7 million genetic variations and highlighted 36 specific genes implicated in bipolar disorder. These genes, prioritized through fine-mapping and variant-to-gene mapping, offer valuable clues about the biological pathways involved. “The newly identified genes may also be used in experiments to explore new drug targets and drug development for bipolar disorder,” said Niamh Mullins, PhD, a senior author and assistant professor at the Icahn School of Medicine at Mount Sinai.
One notable discovery was the identification of an ancestry-specific association within the East Asian cohort, demonstrating the importance of including diverse populations in genetic research. Additionally, the study revealed differences in the genetic profiles of bipolar disorder depending on how participants were recruited—whether from clinical settings, community biobanks, or self-reported surveys. These differences were linked to varying prevalence of bipolar subtypes, underscoring the need for tailored research methodologies.
The genetic signal of bipolar disorder was found to be associated with specific brain cell types, particularly GABAergic interneurons and medium spiny neurons in the prefrontal cortex and hippocampus. Surprisingly, cells in the intestine and pancreas were also implicated, suggesting a broader biological connection that warrants further investigation.
“Although this work does not immediately impact patient care, it opens the possibilities for long-term positive impact for patients and their families,” said Ole Andreassen, MD, PhD, a senior author and professor of psychiatry at the University of Oslo. “Our research paves the way for the development of improved treatments, earlier interventions, and precision medicine approaches.”
This large-scale effort would not have been possible without extensive global collaboration. “This research represents the culmination of efforts from scientists worldwide, enabling the study of hundreds of thousands of DNA sequences,” added Kevin O’Connell, PhD, first author and researcher at the University of Oslo.
By uncovering the genetic underpinnings of bipolar disorder, this study marks a significant step toward understanding and treating a condition that imposes a substantial global burden. With its findings, researchers hope to accelerate the development of therapies that can better address the needs of individuals living with bipolar disorder.
