Scientists have identified dozens of previously unidentified genetic indicators that increase risk for bipolar disorder, in what scientists say is the largest study of its kind to date. In a genome-wide association study (GWAS) involving over 400,000 people – some 41,917 of whom had bipolar disorder – scientists compared variants in participants' DNA, looking for genetic markers that might be tied to the occurrence of the condition. Bipolar disorder is a heritable mental disorder characterized by severe mood swings, typically ranging from mania or hypomania to depression; it's estimated to affect about 45 million people across the globe. While it has several subtypes, the condition is usually lifelong, and people with bipolar disorder also tend to have an increased risk of dying from suicide; it's one of the reasons why a better understanding of the disease, including its genetic underpinnings, is a major public health concern. "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 psychiatric geneticist Niamh Mullins from the Icahn School of Medicine at Mount Sinai in New York. Previous GWAS investigations into the genetic origins of bipolar disorder have transformed our understanding of the condition by revealing numerous gene variants involved. Despite these advancements, we're still very much at the beginning of this journey into figuring out how genes – including those shared by family members – affect people's chances of developing bipolar disorder, let alone appreciating how environmental factors may also contribute. "Only a fraction of the genetic etiology of bipolar disorder has been identified, and the specific biological mechanisms underlying the development of the disorder are still unknown," Mullins and her co-authors explain in their new paper. In the latest work, Mullins and her team more than doubled the existing count of known genetic markers for bipolar disorder, identifying 64 regions in the genome containing DNA variations that increase risk, 33 of which are new to science. "Our study found DNA variations involved in brain cell communication and calcium signaling that increase risk of bipolar disorder," Mullins says. Amongst the total 64 genomic loci associated with increased risk, 17 have previously been tied to the development of schizophrenia, while seven are linked to major depression – a coincidence that the researchers say represents "the first overlap of genome-wide significant loci between the mood disorders". While there's still much we have yet to tease out in the data, the modeling here could suggest that some variants may put individuals at an increased risk of developing different kinds of depressive conditions. "Across the entire genome, almost all variants influencing bipolar disorder also influence schizophrenia and major depression, albeit with variable effects," the team writes. "Our results also corroborate previous genetic and clinical evidence of associations between bipolar and sleep disturbances, problematic alcohol use, and smoking." In addition, the results appear to confirm previous indications that the two sub-types of bipolar (I and II) are genetically based, with BD I correlated with schizophrenia, while BD II has stronger genetic ties to major depression. Ultimately, the researchers hope that the new and confirmed genetic correlations could help us to identify the most suitable candidate genes that could be targeted by future forms of medication. That future is not here yet, but thanks to these scientists, we just took another stride towards it. The findings are reported in Nature Genetics. Source
