title: Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.
abstract: The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Biomedical Centre, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Wilbe
authors.forename: Päivi
authors.initials: P
authors.lastname: Jokinen
authors.forename: Katarina
authors.initials: K
authors.lastname: Truvé
authors.forename: Eija H
authors.initials: EH
authors.lastname: Seppala
authors.forename: Elinor K
authors.initials: EK
authors.lastname: Karlsson
authors.forename: Tara
authors.initials: T
authors.lastname: Biagi
authors.forename: Angela
authors.initials: A
authors.lastname: Hughes
authors.forename: Danika
authors.initials: D
authors.lastname: Bannasch
authors.forename: Göran
authors.initials: G
authors.lastname: Andersson
authors.forename: Helene
authors.initials: H
authors.lastname: Hansson-Hamlin
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics; D001167:Arteritis / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003095:Collagen Diseases / Q000150:complications / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics*; D008581:Meningitis / Q000150:complications / Q000235:genetics; D008954:Models, Biological; D012216:Rheumatic Diseases / Q000150:complications / Q000235:genetics
chemical_list: D000974:Antibodies, Antinuclear