title: ADAM23 is a common risk gene for canine idiopathic epilepsy.
abstract: Idiopathic or genetic adult-onset epilepsy is a common neurological disorder in domestic dogs. Genetic association has been reported only with ADAM23 on CFA 37 in few breeds. To identify novel epilepsy genes, we performed genome-wide association (GWA) analyses in four new breeds, and investigated the association of the previously reported ADAM23 haplotype with the epilepsy phenotype in eight breeds.
  
  
  
  GWA analysis did not reveal new epilepsy loci. ADAM23 association (p < 0.05) was identified in five breeds. Combined analysis of all eight breeds showed significant association (p = 4.6e-6, OR 1.9).
  
  
  
  Our results further support the role of ADAM23 in multiple breeds as a common risk gene for epilepsy with low penetrance. The lack of findings in the GWA analyses points towards inefficient capture of genetic variation by the current SNP arrays, causal variant(s) with low penetrance and possible phenocopies. Future work will include studies on ADAM23 function and expression in canine neurons, as well as whole-genome sequencing in order to identify additional IE genes.
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Lotta L E
authors.initials: LL
authors.lastname: Koskinen
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Eija H
authors.initials: EH
authors.lastname: Seppälä
authors.affiliation: Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Weissl
authors.affiliation: Department of Clinical Veterinary Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Tarja S
authors.initials: TS
authors.lastname: Jokinen
authors.affiliation: Department of Clinical Veterinary Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Ranno
authors.initials: R
authors.lastname: Viitmaa
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences and Department of Medical Genetics, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Reetta L
authors.initials: RL
authors.lastname: Hänninen
authors.affiliation: CNRS, UMR 6290, Institut de Génétique et Développement de Rennes, Rennes, France.|Université Rennes 1, UEB, Biosit, Faculté de Médecine, Rennes, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Quignon
authors.affiliation: Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Fischer
authors.affiliation: CNRS, UMR 6290, Institut de Génétique et Développement de Rennes, Rennes, France.|Université Rennes 1, UEB, Biosit, Faculté de Médecine, Rennes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: André
authors.affiliation: Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland. hannes.lohi@helsinki.fi.|Department of Veterinary Biosciences and Department of Medical Genetics, University of Helsinki, Helsinki, Finland. hannes.lohi@helsinki.fi.|Folkhälsan Institute of Genetics, Helsinki, Finland. hannes.lohi@helsinki.fi.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D004827:Epilepsy / Q000235:genetics / Q000662:veterinary*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D023281:Genomics; D006239:Haplotypes / Q000235:genetics; D019683:Penetrance; D010641:Phenotype
chemical_list: D051722:ADAM Proteins
keywords: ADAM23; Association; Canis familiaris; Dog; Epilepsy; GWA; Idiopathic epilepsy