In the largest genetic study of bipolar disorder to date, researchers have identified 64 regions of the genome containing DNA variations that increase risk of this condition – more than double the number previously identified. Bipolar disorder is known to be one of the most heritable mental illnesses, but unravelling the genetics of this condition has been challenging.

The research team also found overlap in the genetic bases of bipolar disorder and other psychiatric disorders. Furthermore, the study supports a role of sleep habits, alcohol, and substance usage in the development of bipolar disorder. Their study results were published today in Nature Genetics. http://dx.doi.org/10.1038/s41588-021-00857-4 

“It is well-established that bipolar disorder has a substantial genetic basis and identifying DNA variations that increase risk can yield insights into the condition’s underlying biology,” says Niamh Mullins, Ph.D., Assistant Professor of Psychiatric Genomics at the Icahn School of Medicine at Mount Sinai and lead author of the paper. “Our study found DNA variations involved in brain cell communication and calcium signaling that increase risk of bipolar disorder.”

Bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of severely high and low mood, and affects an estimated 40 to 50 million people worldwide. It typically begins in young adulthood, often takes a chronic course, and carries an increased risk of suicide, making it a major public health concern and cause of global disability. It is associated with substance abuse, as well as other psychiatric disorders such as anxiety, eating disorders, and chronic affective symptoms. It’s estimated that in the US alone, this condition leads to $31 billion in direct costs and $120 billion in indirect costs.

More than 1,300 clinical trials are currently ongoing for treatments of bipolar disorder.

To help elucidate the underlying biology of this condition, an international team of scientists from within the Psychiatric Genomics Consortium conducted a genome-wide association study. This involved scanning more than 7.5 million common variations in the DNA sequence of nearly 415,000 people, more than 40,000 of whom had bipolar disorder. The study identified 64 regions of the genome containing DNA variations that increase risk of bipolar disorder.

These findings suggest that drugs, such as calcium channel blockers, already used for the treatment of high blood pressure and other conditions of the circulatory system, could be potential treatments for bipolar disorder.

The study also found overlap in the genetic basis of bipolar disorder and that of other psychiatric disorders and confirmed the existence of partially genetically distinct subtypes of the disorder. Specifically, they found that bipolar I disorder shows a strong genetic similarity with schizophrenia and bipolar II disorder is more genetically similar to major depression.

“This research would not have been possible without the collaborative efforts of scientists worldwide that enabled the study of hundreds of thousands of DNA sequences,” said Ole Andreassen, MD, PhD, Professor of Psychiatry, Institute of Clinical Medicine and Oslo University Hospital and senior author of the paper. “Through this work, we prioritized some specific genes and DNA variations which can now be followed up in laboratory experiments to better understand the biological mechanisms through which they act to increase risk of bipolar disorder.”

The researchers say that further genetic studies in larger and more diverse populations are needed to pinpoint the genes relevant to risk of bipolar disorder in other areas of the genome.

The Psychiatric Genomics Consortium (PGC) is an international consortium of scientists dedicated to studying the genetic basis of psychiatric disorders and includes over 800 researchers, from more than 150 institutions from over 40 countries.