Researchers have found that common genetic variants may significantly influence epilepsy occurrence and severity in families previously thought to have single-gene causes, according to a new study.

In the study, published in eBioMedicine, the researchers examined 304 individuals from 58 families with genetic epilepsy with febrile seizures plus (GEFS+). For each standard deviation increase in epilepsy polygenic risk score (PRS), relatives were 40% more likely to develop epilepsy.

Individuals in the highest decile of epilepsy PRS were 3.5 times more likely to have an epilepsy diagnosis compared with other relatives.

The researchers found that relatives with more severe phenotypes had a higher PRS compared with family members with milder symptoms, with a mean pairwise PRS difference of + 0.19.

Two specific genetic variants showed different patterns. The GABRG2 p.Arg82Gln variant showed strong correlation between a higher PRS and increased phenotype severity, whereas the SCN1B p.Cys121Trp variant did not show significant correlation.

The study had several limitations, including small sample size and restriction to individuals of European ancestry. The researchers noted that the epilepsy PRS may not be ready for clinical application.

The National Health and Medical Research Council of Australia and the Medical Research Future Fund of Australia supported this research, which was conducted by investigators from multiple institutions including the Walter and Eliza Hall Institute of Medical Research.

Conflict of interest disclosures can be found in the study.