title: Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.
abstract: Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Siobhan
authors.identifier: 0000-0003-4139-6622
authors.initials: S
authors.lastname: Simpson
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Dunning
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Serena
authors.initials: S
authors.lastname: Brownlie
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Janika
authors.identifier: 0000-0002-1750-4366
authors.initials: J
authors.lastname: Patel
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Megan
authors.identifier: 0000-0002-1855-3063
authors.initials: M
authors.lastname: Godden
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Malcolm
authors.identifier: 0000-0001-5756-063X
authors.initials: M
authors.lastname: Cobb
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK; Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Nigel P
authors.identifier: 0000-0001-5438-1126
authors.initials: NP
authors.lastname: Mongan
authors.affiliation: Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
authors.forename: Catrin S
authors.identifier: 0000-0002-2009-4898
authors.initials: CS
authors.lastname: Rutland
mesh_terms: D000483:Alleles; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis / Q000235:genetics / Q000662:veterinary*; D015331:Cohort Studies; D004283:Dog Diseases / Q000175:diagnosis / Q000235:genetics*; D004285:Dogs; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity