Companion animals

Genome-wide association analysis of acquired urinary incontinence in female dogs

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Abstract

Urethral sphincter mechanism incompetence (USMI) is the most common acquired urinary incontinence (UI) in adult female dogs. Although the loss of reproductive hormones after ovariohysterectomy surgery (spay) is considered one of the major risk factors, the fact that breed-specific predisposition exists suggests a genetic contribution to USMI. However, the current research has not addressed the underlying genetic predisposition of this complex trait. Our objective is to identify genetic associations with USMI in two different populations of female dogs. We used data from two longitudinal studies, the Morris Animal Foundation Golden Retriever Lifetime Study (GRLS) and the Dog Aging Project (DAP). Cases were spayed female dogs with a reported diagnosis of UI. Because UI is a symptom of multiple conditions, we reviewed medication data (GRLS) and owner comments (DAP) to include only dogs with a USMI diagnosis. Controls in both datasets were spayed females, ≥10 years of age, with no history of urinary disease. Single nucleotide polymorphism (SNP) data underwent quality control filtering in Plink v. 2.0. A linear mixed model genome-wide association study (GWAS) was performed using R package 'gaston' v. 1.6. GWASs were conducted separately for each dataset due to the different genotyping methods used (chip vs. low pass WGS) and to avoid population stratification/bias from merging golden retrievers (GRLS) with a diverse breed cohort (DAP). The DAP cohort included 65 purebred and 145 mixed breed dogs with ancestry from >45 breeds represented overall. Genome-wide significance was determined using a Bonferroni correction for the calculated number of independent variants in the population using Plink. A conventionally used suggestive threshold (P2>0.5) with top SNPs were defined using results-based LD clumping in Plink. After performing quality control in each cohort, the GRLS dataset included 23 cases and 756 controls with 487,885 SNPs and threshold for significance set at 3.8E-07. The DAP dataset included 51 cases and 159 controls with 6,961,186 SNPs and threshold for significance set at 2.6E-08. There were no associations that passed the stringent threshold for genome-wide significance in either dataset. The top two loci identified in the GRLS cohort overlapped genes linked to extracellular matrix: NAALADL2 (N-Acetylated Alpha-Linked Acidic Dipeptidase Like 2) and PCOLCE2 (Procollagen C-Endopeptidase Enhancer 2) (P=6.7E-07 and P=1.6E-06, respectively). In the DAP cohort, the top locus was an intergenic region on chromosome 12 and the second locus was within the boundaries of an uncharacterized long noncoding RNA on chromosome 21 (P=1.1E-06 and P=1.3E-06, respectively). In conclusion, these exploratory findings suggest that genetic risk of USMI in female dogs may be related to connective tissue architecture and function. Further research is needed to validate these associations.

Keywords: 2026

How to Cite:

Baker, L. & Valdes-Arciniega, T., (2026) “Genome-wide association analysis of acquired urinary incontinence in female dogs”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2285589. doi: https://doi.org/10.31274/wcgalp.23745

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