Genome-wide linkage disequilibrium mapping of susceptibility genes for idiopathic generalized epilepsy

• Applicant: Dr. Thomas Sander
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 35593137

Idiopathic generalized epilepsies (IGEs) affect about 0.2% of the general population and account for 30% of all epilepsies. Genetic factors play a predominant role in the etiology of common IGE syndromes. However, the vast majority of IGE patients display a polygenic etiology. Genome-wide association (GWA) studies have been advocated as the method of choice to search for common susceptibility variants in genetically complex traits. Our ongoing GWA study will comprise 1500 IGE patients and 2000 ethnically matched controls. Given the accumulating evidence emphasizing the impact of structural genomic variants on disease susceptibility, we will extend the GWA study to genomewide analysis of copy number variations (CNVs) using the novel Affymetrix Genome- Wide Human SNP Array 6.0. Our preliminary results suggest that recurrent microdeletions previously associated with neuropsychiatric disorders also increase risk to IGE. The proposed project will explore the impact of CNVs on the genetic etiology of common IGE syndromes. By joint GWA analysis of both SNPs and CNVs, we will enhance prospects to specify individual risk profiles and to differentiate molecular pathways of epileptogenesis for the development of rational treatment strategies.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Peter Nürnberg