New study reports 64 risk genes for bipolar disorder
In a large international study published in Nature Genetics, researchers at NORMENT have identified novel genetic risk variants for bipolar disorder.
Bipolar disorder is a complex psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. The disorder affects almost 50 million people worldwide. Taking into consideration that the condition is widespread, has typical onset in young adulthood, often takes a chronic course, and carries with it an increased risk of suicide, bipolar disorder is a major public health concern and a major cause of global disability.
In the largest genetic study of bipolar disorder to date, researchers within the Psychiatric Genomics Consortium have identified 64 regions of the genome containing DNA variations that increase risk of bipolar disorder - more than double the number of regions previously identified. The research team also found overlap in the genetic basis of bipolar disorder and that of other psychiatric disorders. The results were published in the prestigious scientific journal Nature Genetics on May 17. Several researchers from NORMENT contributed to the work, which was headed by Centre leader Ole A. Andreassen.
The researchers explored the human genome through a "genome-wide association study". This approach involves scanning the genes from many different people and looking for genetic markers that occur at a higher frequency in the presence of a disease. More than 7.5 million common variations in the DNA sequence of nearly 415,000 people were investigated, including more than 40,000 with bipolar disorder.
The results showed that DNA variations involved in neuronal communication and calcium signaling increase the risk of bipolar disorder. This suggests that drugs such as calcium channel blockers that are already used for the treatment of high blood pressure may be appropriate to study for potential use in bipolar disorder.
The team of researchers 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 (including mania) shows a strong genetic similarity with schizophrenia, while bipolar II disorder (including hypomania) is more genetically similar to major depression. Finally, the study suggests a potential causal relationship between bipolar disorder and sleep habits, alcohol and substance usage, although further research is needed to confirm those findings.
The reported genes and DNA variations can now be followed up on in laboratory experiments to better understand the biological mechanisms through which they act to increase risk of bipolar disorder. Ultimately, the findings can lead to the development of new and improved treatments or precision medicine possibilities to stratify patients at high genetic risk who may benefit from targeted treatment or intervention strategies. Understanding causal risk could also aid clinical decision making in the prevention or management of the illness.
Mullins et al. (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology, Nature Genetics, May 17