Genome-Wide Association Study Identifying a Novel Gene Related to a History of Febrile Convulsions in Patients With Focal Epilepsy

Abstract

Background and purpose: The risk factors for developing epilepsy following febrile convulsion (FC) have been studied extensively, but the underlying genetic components remain largely unexplored. Our objective here was to identify the risk loci related to FC through a genome-wide association study of Korean epilepsy patients.

Methods: We examined associations between a history of FC and single-nucleotide polymorphisms (SNPs) in data obtained from 125 patients with focal epilepsy: 28 with an FC history and 97 without an FC history.

Results: Among 288,394 SNPs, 5 candidate SNPs showed p<1×10⁻⁴. Regional association plots of these SNPs identified a novel locus adjacent to PROX1 that is implicated in hippocampal neurogenesis and epileptogenesis. The allele frequencies of the SNPs upstream of PROX1 including two candidate SNPs (rs1159179 and rs7554295 on chromosome 1) differed significantly between the groups with and without an FC history. In contrast, the allele frequencies of the SNPs inside PROX1 showed no differences, indicating dysregulated expression of PROX1 rather than a functional alteration in the PROX1 protein.

Conclusions: This novel discovery of SNPs upstream of PROX1 suggests that the dysregulated expression of PROX1 contributes to the development of focal epilepsy following FC. We propose that these SNPs are potential genetic markers for focal epilepsy following FC, and that PROX1 represents a potential therapeutic target of antiseizure medications.