Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex

Maria Wilbe; Päivi Jokinen; Katarina Truvé; Eija H. Seppala; Elinor K. Karlsson; Tara Biagi; Angela Hughes; Danika L Bannasch; Göran Andersson; Helene Hansson-Hamlin; Hannes Lohi; Kerstin Lindblad-Toh

doi:10.1038/ng.525

Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex

Maria Wilbe, Päivi Jokinen, Katarina Truvé, Eija H. Seppala, Elinor K. Karlsson, Tara Biagi, Angela Hughes, Danika L Bannasch, Göran Andersson, Helene Hansson-Hamlin, Hannes Lohi, Kerstin Lindblad-Toh

Population Health and Reproduction

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

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.

Original language	English (US)
Pages (from-to)	250-254
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	3
DOIs	https://doi.org/10.1038/ng.525
State	Published - Mar 2010

ASJC Scopus subject areas

Genetics

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Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. / Wilbe, Maria; Jokinen, Päivi; Truvé, Katarina; Seppala, Eija H.; Karlsson, Elinor K.; Biagi, Tara; Hughes, Angela; Bannasch, Danika L; Andersson, Göran; Hansson-Hamlin, Helene; Lohi, Hannes; Lindblad-Toh, Kerstin.

In: Nature Genetics, Vol. 42, No. 3, 03.2010, p. 250-254.

Research output: Contribution to journal › Article › peer-review

Wilbe, Maria ; Jokinen, Päivi ; Truvé, Katarina ; Seppala, Eija H. ; Karlsson, Elinor K. ; Biagi, Tara ; Hughes, Angela ; Bannasch, Danika L ; Andersson, Göran ; Hansson-Hamlin, Helene ; Lohi, Hannes ; Lindblad-Toh, Kerstin. / Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. In: Nature Genetics. 2010 ; Vol. 42, No. 3. pp. 250-254.

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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.",

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