Healthcare (Commonwealth Union) – In the largest genome-wide study of bipolar disorder to date, a global team that includes University College London (UCL) researchers have discovered 298 genomic regions with DNA variations that are associated with an increased risk of the condition.
The findings, that appeared in Nature, represent a more than four-fold rise in the number of genetic associations previously identified.
This research marks the first major multi-ancestry genomic analysis of bipolar disorder, incorporating data from individuals of European, East Asian, African American, and Latino descent. It also highlights a new genomic region tied to higher risk for the disorder specifically in East Asian samples. By using a variety of methods, such as fine-mapping and variant-to-gene mapping, the team pinpointed 36 genes thought to play a role in bipolar disorder.
Bipolar disorder is known as a chronic mood disorder that significantly impacts life quality and daily functioning, and it is linked to an increased risk of suicide. It affects an estimated 40-50 million people globally.
Researchers of the study pointed out that bipolar disorder is classified into two main subtypes: Type 1, which involves episodes of both mania and depression, and Type 2, which includes hypomania (a milder form of mania) alongside depression. Although bipolar disorder is relatively common, obtaining an accurate diagnosis can take an average of eight years, and much remains unknown about the biological aspects of the condition.
To shed light on the genetic underpinnings of bipolar disorder, an international team from the Psychiatric Genomics Consortium conducted a large-scale genome-wide association study. They analyzed the DNA of 2.9 million participants worldwide to identify genetic markers more prevalent among individuals with the disorder. This study examined over 6.7 million common genetic variations in the participants’ DNA, more than 158,000 of whom have bipolar disorder.
Professor Andrew McQuillin from UCL Psychiatry, a senior author of the study, pointed out that while current medications for bipolar disorder provide essential relief for many, they are not universally effective. There is a continued need for better treatments. They hope that by enhancing our understanding of the genetic factors involved, they can gain insight into the disorder’s mechanisms and potentially develop new therapies.
Dr. Niamh Mullins from Icahn School of Medicine at Mount Sinai, another senior author, indicated that bipolar disorder’s strong genetic component is well-documented, so pinpointing DNA variations that contribute to the risk is crucial for understanding the condition’s genetic structure. In addition to identifying 298 genomic regions linked to an increased risk of bipolar disorder, they have also found 36 key genes that could be further investigated to explore the biological pathways through which they contribute to the disorder.
“The newly identified genes may also be used in experiments to explore new drug targets and drug development for bipolar disorder.”
The research team revealed that the genetic markers for bipolar disorder are linked to particular types of brain cells, such as GABAergic interneurons and medium spiny neurons, located in the prefrontal cortex and hippocampus of the brain. Interestingly, they also discovered a connection to cells in the intestine and pancreas, although further investigation is needed to fully grasp the biological implications.
Professor Ole Andreassen from the University of Oslo) and a senior author of the paper, says “Although this work does not immediately impact patient care, it opens the possibilities for long-term positive impact for patients and their families who are impacted by this widespread disorder. Our research paves the way for the development of improved treatments, 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.”
