New genes and pathways have been discovered in bipolar disorder

BD, like schizophrenia and other psychiatric disorders, is highly heritable but we've struggled to pinpoint exactly what genes are involved in causing it.

BD comes in two forms: Both are characterized by having bouts with depression but BDI includes mania (abnormally elevated mood or behaviors) and BDII includes hypomania (slightly less elevated, but still elevated, mood/energy).

But our inability to identify genetic causes in BD is pretty frustrating considering the number of people afflicted with the disorder and the fact that genetic tests, like high throughput whole genome sequencing, are now available at a reasonable cost. 

Historically, the field of psychology has relied heavily on performing genome wide association studies (GWAS) in these individuals because this technology is cost effective, and after spending years trying to find a single gene cause for BD (and not finding many), it's been assumed that the disorder is polygenic.

Describing a disorder as polygenic just means that we think more than one gene is contributing to the development of the disorder.

This makes it significantly harder to understand the cause and how to treat it. 

Psychiatry, and GWAS in general, also struggles with the fact that most studies on these disorders are performed in white Europeans so the contributions of genes in more diverse populations has been ignored. 

This potentially has made us miss important contributors and pathways involved in the development of BD.

However, a recent meta analysis of 158,036 individuals with BD and 2,796,499 controls across European, East Asian, African American and Latino ancestries has found 298 new genetic loci linked to BD.

In the figure above, a gene set enrichment analysis was performed and correlated with a recent single-cell RNAseq dataset to determine which neuronal subtypes are most likely to be affected in BD (gray, not associated, orange to red, associated).

The clustering of the data indicate that synaptic neurons, prefrontal cortex and hippocampal interneurons, and hippocampal pyramidal neurons could be important for the development and progression of BD.

In addition to the neuronal cell type association data, they found 36 new genes associated with BD and a drug targeting analysis indicated that at least 16 of them could be good candidates for small molecule therapy.

This study identifies new genetic and neurobiological mechanisms underlying BD which could be used in the development of new treatments or therapies.

However, because this was a meta analysis of SNP based GWAS datasets, there's likely other (rarer or ancestry specific) associations that would be found using more comprehensive genomic methods.