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

Abstract Background Epilepsy is one of the most prevalent neurological disorders, affecting 50 million individuals worldwide. The aetiology of epilepsy is known to have genetic contributions, yet headline results obtained from genome-wide association studies (GWAS) of epilepsy have not always been consistent. We undertook a systematic review of all the findings from this work in order to identify risk variants for epilepsy. Methods This systematic review was conducted in accordance with the updated PRISMA protocol. EbscoHost, PubMed, Scopus, Web of Science and Primo were searched between the years 2010 – 2024. The quality of each of the studies was evaluated using the Q-Genie tool. Results 11 studies were included for full extraction, analysis, and quality assessment. Across the identified studies, 79 SNPs, located in 64 genes, were significantly associated with epilepsy at the genome-wide level. The majority of the variants were intronic and intergenic, with the well documented SCN1A the most widely reported gene involved across studies. Two SNPs, rs2292096 and rs149212747, linked respectively to focal epilepsy (FE) and status epilepticus, were exclusively identified in individuals of Asian ancestry, alongside an Asian-exclusive synonymous variant (rs3782886) in BRAP and a missense variant (rs671) in ALDH2 . Conclusions Genes which encode for ion and transport channels, transcription factors, ubiquitin ligase and transporter proteins were identified as potentially involved in the aetiology of epilepsy disorders. The review identified one missense and one synonymous variant which deserve further exploration. Future research should also include populations of more diverse ancestries as this may reveal unique and important epilepsy-associated genes.