Abstracts

Rationale: A genome wide association study was performed in an attempt to identify susceptibility genes for common forms of human epilepsy. Methods: We genotyped 550,000 single nucleotide polymorphisms (SNPs) in each of 1000 unrelated epilepsy patients (n = 617 with idiopathic generalized epilepsy; n = 383 with focal epilepsy with normal MRI or mesial temporal sclerosis) and 3000 unrelated healthy control subjects all of European ancestry matched for age and gender. Genotyping was performed by The Center for Applied Genomics at The Children's Hospital of Philadelphia using Illumina Infinium technology. Results: Preliminary results using chi square contingency testing and comparing allele frequency in all cases versus all controls identified 19 SNPs (11 in known genes) that reached genome wide significance with a p value of 1x10-7 or lower with the strongest association signal on Chr 6. Another 40 SNPs (16 in known genes) reached a level suggestive of statistical significance with a p value of 1x10-6. Copy number variation (CNV) analysis demonstrated a significant difference in the total number of genome duplications observed in the cases compared to the controls (p = 1x10-4). Preliminary results reveal that a number of genes related to processes of biological development are associated with epilepsy. Conclusions: We conclude that the genome wide association study has identified genetic variation that is correlated with common forms of epilepsy. Future analysis will concentrate on replication of these findings in an independent cohort, identifying and eliminating false positive results, comparing control subjects to generalized and focal epilepsy patients separately, enhancing the CNV analysis, and separating the patients into groups based on efficacy and tolerability of antiepileptic drugs.