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

Research output: Contribution to journalArticle

84 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)250-254
Number of pages5
JournalNature Genetics
Volume42
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Systemic Lupus Erythematosus
Canidae
Genome
Dogs
Nova Scotia
Arteritis
Inborn Genetic Diseases
Ducks
Genome-Wide Association Study
Antinuclear Antibodies
Linkage Disequilibrium
Rheumatic Diseases
Meningitis
Single Nucleotide Polymorphism
Steroids
Incidence

ASJC Scopus subject areas

  • Genetics

Cite this

Wilbe, M., Jokinen, P., Truvé, K., Seppala, E. H., Karlsson, E. K., Biagi, T., ... Lindblad-Toh, K. (2010). Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nature Genetics, 42(3), 250-254. https://doi.org/10.1038/ng.525

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 journalArticle

Wilbe, M, Jokinen, P, Truvé, K, Seppala, EH, Karlsson, EK, Biagi, T, Hughes, A, Bannasch, DL, Andersson, G, Hansson-Hamlin, H, Lohi, H & Lindblad-Toh, K 2010, 'Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex', Nature Genetics, vol. 42, no. 3, pp. 250-254. https://doi.org/10.1038/ng.525
Wilbe M, Jokinen P, Truvé K, Seppala EH, Karlsson EK, Biagi T et al. Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nature Genetics. 2010 Mar;42(3):250-254. https://doi.org/10.1038/ng.525
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.
@article{eadfa810f1fc46baacec456df7eee8cf,
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.",
author = "Maria Wilbe and P{\"a}ivi Jokinen and Katarina Truv{\'e} and Seppala, {Eija H.} and Karlsson, {Elinor K.} and Tara Biagi and Angela Hughes and Bannasch, {Danika L} and G{\"o}ran Andersson and Helene Hansson-Hamlin and Hannes Lohi and Kerstin Lindblad-Toh",
year = "2010",
month = "3",
doi = "10.1038/ng.525",
language = "English (US)",
volume = "42",
pages = "250--254",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex

AU - Wilbe, Maria

AU - Jokinen, Päivi

AU - Truvé, Katarina

AU - Seppala, Eija H.

AU - Karlsson, Elinor K.

AU - Biagi, Tara

AU - Hughes, Angela

AU - Bannasch, Danika L

AU - Andersson, Göran

AU - Hansson-Hamlin, Helene

AU - Lohi, Hannes

AU - Lindblad-Toh, Kerstin

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77649188325&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649188325&partnerID=8YFLogxK

U2 - 10.1038/ng.525

DO - 10.1038/ng.525

M3 - Article

VL - 42

SP - 250

EP - 254

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -