A GROUNDBREAKING study has recently uncovered genetic factors that could revolutionise the treatment of epilepsy. The study, conducted by the Epi25 Collaborative, is the largest and most diverse of its kind, involving over 54,000 participants from varied genetic backgrounds.
Epilepsy, a common neurological disorder affecting millions globally, has long been associated with genetic risks. However, the complex interplay of genes contributing to its various subtypes has made it challenging to identify specific genetic markers. This new research not only sheds light on shared and subtype-specific genetic variations but also points to potential targets for tailored therapies.
This research utilised whole exome sequencing to examine the protein-coding regions of participants’ genomes. The team focused on “ultra-rare” variants (URV) – genetic mutations occurring in fewer than one in 10,000 people.
Among the significant findings, researchers identified genes linked to how neurons communicate across synapses. Variations in ion channel proteins, such as GABAA receptors, were found to play a pivotal role in epilepsy across subtypes. For example, a strong genetic signal was observed in patients with non-acquired focal epilepsy (NAFE) for the gene DEPDC5, which forms part of the GATOR1 protein complex crucial to brain cell function. Aggregating data from genes within the same protein complexes, like GATOR1, amplified the findings, highlighting potential mechanisms driving specific epilepsy subtypes.
The study’s results could pave the way for more precise treatments, enabling doctors to tailor therapies to an individual’s genetic profile. It may also improve genetic testing and deepen understanding of the biological pathways underlying epilepsy.
“These genetic insights provide data-driven starting points for unravelling the biology of epilepsies,” commented the authors. “This could spur future, subtype-tailored advances in diagnosis and treatment.”
Summary data from the research is accessible via the Epi25 WES Browser, allowing clinicians to explore genetic variants in their patients and fostering further research.
Reference
Epi25 Collaborative. Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes. Nat Neurosci. 2024;27(10):1864-79.
