Genome-wide rare copy number variations potentially associated with drug resistance in epilepsy.

Epilepsy is a common neurological disorder with a strong genetic component. Copy number variations (CNVs) are structural genomic alterations that contribute to normal genomic variation as well as disease phenotypes. Persons with epilepsy reportedly carry a greater CNV burden compared to healthy individuals. These variations often affect crucial epileptogenic genes and pathways and may contribute to drug-resistant epilepsy (DRE) which affects one-third of epilepsy patients. However, data on CNVs in DRE is scarce. We used whole genome sequencing technique (10X) to obtain the genomic data of 109 subjects diagnosed with drug-refractory epilepsy (DRE; n = 64) or drug-sensitive epilepsy (DSE; n = 45) and identified five rare exonic autosomal CNVs potentially associated with DRE. Bioinformatics-based analyses indicate that these CNVs may affect several genes, including a number of genes previously reported in epilepsy, general drug response genes, and genes with significant neurobiological roles. Biostatistical analyses show that some CNVs are associated with a lower age of onset of seizures or higher seizure frequency at statistically significant levels. Taken together, the results indicate that rare CNVs may contribute to DRE and highlight genomic variants that are suitable candidates for further evaluation as pharmacogenomic biomarkers and potential future therapeutic targets.