Epilepsy Essentials: Research Deepens Understanding of Genetics and Epilepsy

Genes that may contribute to epilepsy have been identified in a new analysis of 34,000 people worldwide. According to recent study published in Lancet Neurology (13(9): 893 – 903) and reported by investigators at Royal Melbourne Hospital, the sodium channel subunit that regulates neuronal excitability (SCN1A)—previously associated with certain familial and severe childhood epilepsies—may have an even broader role, while a gene for the protein protocadherin is also strongly associated with epilepsy.

The multinational world-wide study—including researchers from Europe, Asia, and North America—was convened by the International League Against Epilepsy. Investigators combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. Individuals with epilepsy were phenotyped into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. Researchers then conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy with the genome-wide significance threshold at p<1·66 × 10−8.

“The data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype,” the authors write. “Future genetic analyses might benefit from both lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of specific clinical subtypes).”

IN CONTEXT

The Royal Melbourne Hospital’s (RMH) epilepsy specialist and Head of the University of Melbourne’s Department of Medicine at The RMH, Professor Terence O’Brien, said in a statement that the research findings show that the development of epilepsy may be determined by the combination of inherited genes. “We knew there was a genetic link to developing epilepsy but this latest study identifies two specific genes that we believe may be strong contributors to epilepsy, one of which had not previously been implicated in the cause of epilepsy,” Professor O’Brien said. “Every new piece of research undertaken is another exciting step to developing better treatments for people with epilepsy, better patient care and hopefully in the future solving this puzzle completely.”

Professor Samuel Berkovic, from the Austin Hospital and the University of Melbourne, who led the international consortium, said in a statement that the findings were unexpected. “The findings suggest that the factors that contribute to common epilepsies are more complex than originally thought, and may involve the basic structure of the brain,” he said.

Professor Samuel Berkovic, from the Austin Hospital and the University of Melbourne, who led the international consortium, said in a statement that the findings were unexpected. “The findings suggest that the factors that contribute to common epilepsies are more complex than originally thought, and may involve the basic structure of the brain,” he said.

“For years we have focused on those genes that regulate the excitability of the brain,” Professor Berkovic said. “Findings such as these really turn our concepts on their head. It was a really exciting finding that will now be used to spearhead further research in this area.”