Systematic review of genome wide association studies (GWAS) of epilepsy identifies common risk variants and associated genes

Abstract

AbstractEpilepsy is one of the most prevalent neurological disorders, affecting 50 million individuals worldwide. The aetiology of epilepsy is known to have genetic contributions, yet the results obtained from genome-wide association studies (GWAS) conducted on epilepsy lack consistency. Therefore, it may be useful to conduct a systematic review of the existing research. The objective of this study was to systematically review GWAS for epilepsy to identify risk variants for this disorder. This systematic review was conducted in accordance with the updated PRISMA protocol. The quality of each of the studies was evaluated using the Q-Genie tool. A total of 10 studies were included for the full extraction, analysis, and quality assessment. Across the identified studies, 51 SNPs, located in 39 genes, were significantly associated with epilepsy at the genome-wide level. Several of these significant SNPs are located in ion channel genes. Three genes, in particular,SCN1A,PADI6andFANCL, had the highest number of associated SNPs. BothSCN1AandFANCLwere found to be associated with several epilepsy subtypes, including generalized and focal epilepsy syndromes.PADI6was associated with generalized epilepsy only. Genes which encode for ion and transport channels, transcription factors, ubiquitin ligase and transporter proteins were identified as genes which may be involved in the aetiology of epilepsy disorders and should be further explored. Future research should also include populations of more diverse ancestries as this may reveal unique and important epilepsy-associated genes.