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. 2020 Nov 26;21(1):833.
doi: 10.1186/s12864-020-07243-0.

Genetic characterization of Addison's disease in Bearded Collies

Liza C Gershony  1   2 , Janelle M Belanger  1 , Marjo K Hytönen  3 , Hannes Lohi  3 , Thomas R Famula  1 , Anita M Oberbauer  4
Affiliations

Genetic characterization of Addison's disease in Bearded Collies

Liza C Gershony et al. BMC Genomics. .

Erratum in

Abstract

Background: Primary hypoadrenocorticism (or Addison's disease, AD) is an autoimmune disease that results in destruction of the adrenal cortex and consequent adrenal insufficiency. The disease has been described in purebred and mixed breed dogs, although some breeds, including the Bearded Collie, are at increased risk for AD. Candidate gene approaches have yielded few associations that appear to be breed-specific. A single other genome-wide association study reported no significant regions of association for AD in Standard Poodles. The present study aimed to identify genomic regions of association for canine AD in Bearded Collies.

Results: Our study consists of the first genome-wide association analysis to identify a genome-wide significant region of association with canine AD (CFA18). Peaks of suggestive association were also noted on chromosomes 11, 16 and 29. Logistic regression analysis supported an additive effect of risk genotypes at these smaller effect loci on the probability of disease associated with carrying a risk genotype on CFA18. Potential candidate genes involved in adrenal steroidogenesis, regulation of immune responses and/or inflammation were identified within the associated regions of chromosomes 11 and 16. The gene-poor regions of chromosomes 18 and 29 may, however, harbor regulatory sequences that can modulate gene expression and contribute to disease susceptibility.

Conclusion: Our findings support the polygenic and complex nature of canine AD and identified a strongly associated locus on CFA18 that, when combined with three other smaller effect loci, was predictive of disease. The results offer progress in the identification of susceptibility loci for canine AD in the Bearded Collie. Further studies are needed to confirm association with the suggested candidate genes and identify actual causative mutations involved with AD susceptibility in this breed.

Keywords: Addison’s disease; Autoimmune; Dogs; GWAS; Genomics; Hypoadrenocorticism.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Manhattan Plots
Fig. 2
Fig. 2
Number of Risk Genotypes in Case and Control Bearded Collies. Number of SNPs containing risk genotypes for Addison’s disease (AD) in 140 Bearded Collies (55 AD cases, 85 controls)
Fig. 3
Fig. 3
Location of Haplotype Blocks Associated with Addison’s Disease in Bearded Collies. Diagram showing the top GWAS SNPs and location of haplotype blocks on (A) CFA11, (B) CFA16, (C) CFA18 and (D) CFA29. No haplotype blocks were associated with Addison’s disease on CFA29. Top GWAS SNPs in each chromosome are listed in red
See this image and copyright information in PMC

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