The complex genetics of epilepsies

Our research interests focus on the identification of genetic risk factors underlying epilepsies. Although the aetiology of epilepsies is multifactorial, there is certainly a large heritable component in the range of 70% to 90% for the clinically common phenotypes. Only a small proportion of the heritability can be attributed to known Mendelian (monogenic) disorders. The vast majority of the heritability is still unknown and thought to be caused by either common or rare genetic variants with smaller effect sizes. Our ultimate goal is to identify these risk factors and to understand the complex genetic architecture of common epilepsies. To achieve this goal we genotype and sequence candidate genes or whole genomes/exomes of patients with epilepsies. We are in close cooperation with international consortia on epilepsy genetics

Techniques

State of the art genotyping (various techniques including SNP-arrays), conventional Sanger sequencing as well as next generation sequencing methods. A large part of the work includes recruiting and clinically characterizing patients.

Selected Publications

Hilger E, Reinthaler EM, Stogmann E, Hotzy C, Pataraia E, Baumgartner C, Zimprich A, Zimprich F. Lack of association between ABCC2 gene variants and treatment response in epilepsy. Pharmacogenomics. 2012 Jan;13(2):185-90.

EPICURE Consortium; EMINet Consortium, Steffens M, …Zimprich F, … Koeleman BP, Sander T. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32. Hum Mol Genet. 2012 Dec 15;21(24):5359-72.

Schlachter K, Gruber-Sedlmayr U, Stogmann E, Lausecker M, Hotzy C, Balzar J, Schuh E, Baumgartner C, Mueller JC, Illig T, Wichmann HE, Lichtner P, Meitinger T, Strom TM, Zimprich A, Zimprich F. A splice site variant in the sodium channel gene SCN1A confers risk of febrile seizures. Neurology. 2009 Mar 17;72(11):974-8

Zimprich F, Stogmann E, Bonelli S, Baumgartner C, Mueller JC, Meitinger T,Zimprich A, Strom TM. A functional polymorphism in the SCN1A gene is not associated with carbamazepine dosages in Austrian patients with epilepsy. Epilepsia. 2008 Jun;49(6):1108-9.

Zimprich F, Sunder-Plassmann R, Stogmann E, Gleiss A, Dal-Bianco A, Zimprich A, Plumer S, Baumgartner C, Mannhalter C. Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy. Neurology. 2004 Sep 28;63(6):1087-