A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12
2015 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 10, no 8, e0134720Article in journal (Refereed) Published
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 similar to 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.
Place, publisher, year, edition, pages
2015. Vol. 10, no 8, e0134720
IdentifiersURN: urn:nbn:se:uu:diva-261959DOI: 10.1371/journal.pone.0134720ISI: 000359353300039PubMedID: 26261983OAI: oai:DiVA.org:uu-261959DiVA: diva2:855580
FunderEU, FP7, Seventh Framework Programme, 201370Swedish Research Council, 2009-3376Swedish Research Council, 2012-2826EU, European Research Council, ERC-2012-StG 310203-K9GenesSwedish Research Council Formas, 2009-1689Swedish Research Council Formas, 2010-629