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A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12

Author

Listed:
  • Matteo Bianchi
  • Stina Dahlgren
  • Jonathan Massey
  • Elisabeth Dietschi
  • Marcin Kierczak
  • Martine Lund-Ziener
  • Katarina Sundberg
  • Stein Istre Thoresen
  • Olle Kämpe
  • Göran Andersson
  • William E R Ollier
  • Åke Hedhammar
  • Tosso Leeb
  • Kerstin Lindblad-Toh
  • Lorna J Kennedy
  • Frode Lingaas
  • Gerli Rosengren Pielberg

Abstract

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds—the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018–5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.

Suggested Citation

  • Matteo Bianchi & Stina Dahlgren & Jonathan Massey & Elisabeth Dietschi & Marcin Kierczak & Martine Lund-Ziener & Katarina Sundberg & Stein Istre Thoresen & Olle Kämpe & Göran Andersson & William E R O, 2015. "A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12," PLOS ONE, Public Library of Science, vol. 10(8), pages 1-16, August.
    • Handle: RePEc:plo:pone00:0134720
    DOI: 10.1371/journal.pone.0134720
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    References listed on IDEAS

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    1. Joseph Briggs & Melissa Paoloni & Qing-Rong Chen & Xinyu Wen & Javed Khan & Chand Khanna, 2011. "A Compendium of Canine Normal Tissue Gene Expression," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-12, May.
    2. Erik Axelsson & Abhirami Ratnakumar & Maja-Louise Arendt & Khurram Maqbool & Matthew T. Webster & Michele Perloski & Olof Liberg & Jon M. Arnemo & Åke Hedhammar & Kerstin Lindblad-Toh, 2013. "The genomic signature of dog domestication reveals adaptation to a starch-rich diet," Nature, Nature, vol. 495(7441), pages 360-364, March.
    3. Nadezhda M Belonogova & Gulnara R Svishcheva & Cornelia M van Duijn & Yurii S Aulchenko & Tatiana I Axenovich, 2013. "Region-Based Association Analysis of Human Quantitative Traits in Related Individuals," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-7, June.
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