Abstracts

Although great success has been experienced in mapping genes that harbour causative variants for familial forms of epilepsy, little progress has been made in identifying variants that contribute to the development or treatment of more complex forms of the condition. Several key shortcomings in the study design of previous studies have been identified such as insufficient sample sizes, insufficient coverage of genes and lack of replication of detected associations. Here we attempt to integrate these factors in to the largest genetic mapping study to date in epilepsy., Through the establishment of a multinational collaborative effort, a collection of 3107 epilepsy patients phenotyped for the principal seizure and syndrome types and 1797 healthy controls was assembled. Two hundred and seventy nine candidate genes were selected. For each of these genes bioinformatically-inferred functional variants were identified. Tagging SNPs were also selected for 198 of the 297 genes. In total 4608 SNPs were genotyped using the Illumina Golden Gate platform across all 4904 participants., Preliminary analyses show an enrichment for significant p values (p[lt]0.05) but no one p value is strong enough to withstand correction for multiple testing., This result suggests that the data contain a number of risk factors but the effect of any one of these risk factors is marginal. Data analyses will be enhanced by additional genotyping currently ongoing., (Supported by: This study was funded by the Medical Research Council grant G0400126 and the Programme for Human Genomics funded by the Higher Education Authority of Ireland.)