HQ Team
January 24, 2025: A comprehensive genome-wide association study (GWAS) has found 298 regions containing DNA variations for increased risk of bipolar disorder, a four-fold increase over previous studies.
The researchers from the Psychiatric Genomics Consortium (PGC) analyzed data from 2.9 million individuals, including European, East Asian, African American, and Latino ancestries, to identify genetic markers that were more common in those with the condition. This involved scanning more than 6.7 million common variations in the DNA sequences among the study participants, more than 158,000 of whom had 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, diagnosing the disorder can take an average of eight years. Not much is known about the biology of the disorder.
Gene mapping and DNA variations
The researchers used a range of methods, including fine-mapping and other variant-to-gene-mapping approaches. They identified 36 genes suspected of causing bipolar disorder.
“It is well established that bipolar disorder has a substantial genetic basis, so identifying DNA variations that increase risk is of paramount importance to understanding the condition’s genetic architecture. In addition to identifying 298 regions of the genome that contain variations that increase risk for bipolar disorder, the 36 key genes we identified as being linked to the condition can now be followed up in a range of experiments to uncover the biological mechanisms through which each relates to the disorder,” says Niamh Mullins, PhD, Assistant Professor of Psychiatry, and Genetics and Genomic Sciences, at the Icahn School of Medicine at Mount Sinai and one of the senior authors of the paper.
The genetic signal of bipolar disorder is related to specific brain cell types, including GABAergic interneurons and medium spiny neurons, in the prefrontal cortex and hippocampus. They also found that cells in the intestine and pancreas are involved, although more research is necessary to understand this biology further.
“The newly identified genes may also be used in experiments to explore new drug targets and drug development for bipolar disorder,” emphasized Dr Mullins.
Different genetic profile
The study found differences in the genetic profiles of bipolar disorder recruited from clinical settings, community biobanks or self-reported surveys. These differences were linked to the prevalence of different subtypes of the disorder among the recruiters. This underscores the need for better research methodologies to cover the variances.
One notable discovery was the identification of an ancestry-specific association within the East Asian cohort, again highlighting the need for inclusive studies.
The Psychiatric Genomics Consortium is an international consortium of scientists dedicated to studying the genetic basis of psychiatric disorders and includes more than 1,700 researchers from over 65 countries.
This study marks a significant step toward speeding up the development of therapies that can better address the needs of individuals living with bipolar disorder. Kevin O’Connell, PhD, researcher at the University of Oslo and first author of the paper hopes that the research will help in earlier interventions and precision medicine approaches that will support clinicians in their decision-making to enable them to manage the condition in the most effective way for each patient.
The full study can be found here.
