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

PLoS One. 2015 Aug 11;10(8):e0134720. doi: 10.1371/journal.pone.0134720. eCollection 2015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Dog Diseases / genetics*
  • Dogs
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Haplotypes
  • Hypothyroidism / veterinary*
  • Phenotype
  • Polymorphism, Single Nucleotide

Grants and funding

This work was supported by the European Commission (LUPA), FP7 201370, http://ec.europa.eu/ (MB SD JM ED MK MLZ KS OK GA WERO ÅH TL KLT LJK FL GRP), The Research Council of Norway 207982 and 209909/140, http://www.forskningsradet.no/en/Home_page/1177315753906 (SD MLZ FL), The Norwegian English setter Club, ESNVH2010-001, http://www.nesk.no/ (SD MLZ FL), The Norwegian Gordon setter Club, GSNVH2010-001, http://www.gordonsetter.no/ (SD MLZ FL), The Swedish Research Council, 2009-3376 and 2012-2826, http://www.vr.se/ (MB MK KS OK GA ÅH KLT GRP), European Research Council, ERC-2012-StG 310203-K9Genes, http://erc.europa.eu/ (KLT), The Swedish Research Council Formas, 2009-1689 and 2010-629, http://www.formas.se/ (MB KLT GRP), Agria and Swedish Kennel Club Research, Fund N2011-0039, http://www.skk.se/ and http://www.agria.se/ (MB GRP), American Kennel Club, No: 2447, http://www.akc.org/ (JM WERO LJK), The Albert Heim Foundation, No: 105, http://www.albert-heim-stiftung.ch/ (ED TL).