title: Genome wide high density SNP-based linkage analysis of childhood absence epilepsy identifies a susceptibility locus on chromosome 3p23-p14.
abstract: Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by typical absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to the aetiology is well recognised but the mechanism of inheritance and the genes involved are yet to be fully established. A genome wide single nucleotide polymorphism (SNP)-based high density linkage scan was carried out using 41 nuclear pedigrees with at least two affected members. Multipoint parametric and non-parametric linkage analyses were performed using MERLIN 1.1.1 and a susceptibility locus was identified on chromosome 3p23-p14 (Z(mean)=3.9, p<0.0001; HLOD=3.3, alpha=0.7). The linked region harbours the functional candidate genes TRAK1 and CACNA2D2. Fine-mapping using a tagSNP approach demonstrated disease association with variants in TRAK1.
authors.affiliation: Institute of Child Health, University College London, London, UK. b.chioza@ucl.ac.uk
authors.forename: Barry A
authors.initials: BA
authors.lastname: Chioza
authors.forename: Jean
authors.initials: J
authors.lastname: Aicardi
authors.forename: Harald
authors.initials: H
authors.lastname: Aschauer
authors.forename: Oebele
authors.initials: O
authors.lastname: Brouwer
authors.forename: Petra
authors.initials: P
authors.lastname: Callenbach
authors.forename: Athanasios
authors.initials: A
authors.lastname: Covanis
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dooley
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Martina
authors.initials: M
authors.lastname: Durner
authors.forename: Orvar
authors.initials: O
authors.lastname: Eeg-Olofsson
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.forename: Mogens Laue
authors.initials: ML
authors.lastname: Friis
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Marianne Juel
authors.initials: MJ
authors.lastname: Kjeldsen
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Lina
authors.initials: L
authors.lastname: Nashef
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Auli
authors.initials: A
authors.lastname: Sirén
authors.forename: Elaine
authors.initials: E
authors.lastname: Wirrell
authors.forename: Paul
authors.initials: P
authors.lastname: McKeigue
authors.forename: Robert
authors.initials: R
authors.lastname: Robinson
authors.forename: R Mark
authors.initials: RM
authors.lastname: Gardiner
authors.forename: Kate V
authors.initials: KV
authors.lastname: Everett
mesh_terms: D017668:Age of Onset; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D004832:Epilepsy, Absence / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D018579:Patient Selection; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*