Researchers have identified 64 regions of the human genome associated with a higher risk of developing bipolar disorder. Bipolar disorder is a heritable mental illness with complex etiology that is characterized by extreme mood swings from mania to depression. An estimated 2.8% of adults in the United States have bipolar disorder, with the disorder slightly more common in males than females. An estimated 40-50 million people have the disorder worldwide. Genetic factors are estimated to cause 80% of cases.
Bipolar disorder typically starts in young adulthood. Diagnosis is important as the condition can cause major suffering and is associated with an increased risk of suicide. The ability to identify individuals at risk of developing bipolar disorder could allow interventions that could save lives.
The international team of researchers from the Psychiatric Genomics Consortium (PGC) conducted a genome-wide association study of 41,917 cases of bipolar disorder and 371,549 controls of European ancestry. The study identified 64 genes associated with the disorder – which is more than double the number that had previously been identified. The researchers also found there was some overlap between the genes involved in bipolar disorder and other psychiatric disorders, with 10 of the genes also associated with schizophrenia and also considerable overlap with major depression. There was also an overlap with anorexia, ADHD, and autism spectrum disorder to a lesser degree.
The researchers showed that bipolar disorder type 1 was more closely associated with schizophrenia, while bipolar disorder type 2 was more closely associated with major depression.
According to the researchers, “bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus.”
The researchers identified 15 genes that were robustly linked to bipolar disorder via gene expression, which encoded druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Drugs that are already approved for use for treatments of other conditions such calcium channel blockers that are used to treat high blood pressure and circulatory disorders could potentially be used in the treatment of bipolar disorder and should be explored.
“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.”
You can read more about the study in the paper – Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology – which was recently published in the Nature Genetics. DOI: 10.1038/s41588-021-00857-4