A new genome-wide association study (GWAS) of over 40,000 bipolar disorder cases has provided new insights into the underlying disease biology.
Bipolar disorder
Bipolar disorder is a complex mental disorder that is often characterised by recurrent episodes of mania and depression. Estimates indicate that 40-50 million people worldwide are affected by this disorder. In addition, onset typically occurs in young adulthood and often has a chronic course, with increased risk of suicide. As a result, this makes bipolar disorder a major public health concern and a major cause of global disability.
Bipolar disorder is classified clinically into two main subtypes – bipolar disorder I and bipolar disorder II. Bipolar disorder I involves manic episodes that typically alternate with depressive episodes. Whereas, in bipolar disorder II there is an occurrence of at least one hypomanic and one depressive episode.
Studies have shown that bipolar disorder is a multifactorial disorder, with both genetic and environmental factors contributing to its development. Twin and family studies have specifically estimated that the heritability of bipolar is 60-85%. Moreover, GWASs have led to several valuable insights into the genetic aetiology of the disorder. Despite this progress, only a small proportion of the genetic aetiology has been identified. In addition, the specific biological mechanisms underlying the development of this disorder remain unknown.
Largest GWAS of bipolar disorder to date
In a paper published in Nature Genetics, researchers reported on the findings from the third GWAS meta-analysis of the Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group. The study was comprised of 41,917 individuals with bipolar disorder and 371,549 controls of European ancestry.
From this analysis, the team identified 64 associated genomic loci containing genetic variations that increased the risk of bipolar disorder. These loci were enriched in genes involved in synaptic signalling pathways and brain-expressed genes. These particularly had a high specificity in neurons of the prefrontal cortex and hippocampus. Moreover, they also found significant signal enrichment in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anaesthetics. These findings warrant further research to assess whether medications like calcium channel blockers (which are currently used for treating high blood pressure) would be effective in bipolar. The study also found an overlap in the genetic basis of bipolar disorder and other psychiatric disorders, as well as confirming the existence of the subtypes. For example, bipolar I disorder showed a strong genetic similarity with schizophrenia and bipolar II disorder was more genetically similar to major depression.
Overall, these findings enhance our understanding of the biological aetiology of bipolar disorder. They also provide insights into the development of new and improved treatments that may target high risk genetic groups.
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