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Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs

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Abstract

In humans, genome-wide association studies (GWAS) have been shown to be an effective and thorough approach for identifying polymorphisms associated with disease phenotypes. Here, we describe the first study to perform a genome-wide association study in canine atopic dermatitis (cAD) using the Illumina Canine SNP20 array, containing 22,362 single-nucleotide polymorphisms (SNPs). The aim of the study was to identify SNPs associated with cAD using affected and unaffected Golden Retrievers. Further validation studies were performed for potentially associated SNPs using Sequenom genotyping of larger numbers of cases and controls across eight breeds (Boxer, German Shepherd Dog, Labrador, Golden Retriever, Shiba Inu, Shih Tzu, Pit Bull, and West Highland White Terriers). Using meta-analysis, two SNPs were associated with cAD in all breeds tested. RS22114085 was identified as a susceptibility locus (p?=?0.00014, odds ratio?=?2) and RS23472497 as a protective locus (p?=?0.0015, odds ratio?=?0.6). Both of these SNPs were located in intergenic regions, and their effects have been demonstrated to be independent of each other, highlighting that further fine mapping and resequencing is required of these areas. Further, 12 SNPs were validated by Sequenom genotyping as associated with cAD, but these were not associated with all breeds. This study suggests that GWAS will be a useful approach for identifying genetic risk factors for cAD. Given the clinical heterogeneity within this condition and the likelihood that the relative genetic effect sizes are small, greater sample sizes and further studies will be required.

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Acknowledgement

Biotechnology and Biology Sciences Research Council, Waltham Centre for Pet Nutrition, Pfizer Animal Health, Matthew Settles of Washington State of University who wrote the R script used to generate whole-genome significance plots, and the London and Barts genome Centre for performing the GWAS array.

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Authors and Affiliations

  1. Department of Veterinary Pathology, Faculty of Veterinary Science, The University of Liverpool, Liverpool, L69 3ZJ, UK

    Shona Hiedi Wood & Stuart D. Carter

  2. Centre for Integrated Genomic Medical Research, The Stopford Building, University of Manchester, Manchester, UK

    Shona Hiedi Wood, Xiayi Ke & William E. Ollier

  3. Department of Veterinary Clinical Science, The University of Liverpool, Leahurst Campus, Cheshire, UK

    Tim Nuttall & Neil McEwan

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  1. Shona Hiedi Wood
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  2. Xiayi Ke
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Correspondence to Shona Hiedi Wood.

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Wood, S.H., Ke, X., Nuttall, T. et al. Genome-wide association analysis of canine atopic dermatitis and identification of disease related SNPs. Immunogenetics 61, 765–772 (2009). https://doi.org/10.1007/s00251-009-0402-y

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