Abstract
Purpose :
Glaucoma is a major cause of visual dysfunction in dogs. Additionally, the prevalence of glaucoma has been reported to be higher in dogs than in humans. While genetic factors have been elucidated in humans, they remain poorly understood for canine glaucoma. In this study, we performed a genome-wide association study (GWAS) to elucidate genetic factors of canine glaucoma.
Methods :
We genotyped 123 Shiba-Inus (48 cases, 75 controls) and 58 Shih-Tzus (18 cases, 40 controls) using the Infinium CanineHD BeadChip (Illumina) for 167,183 single nucleotide polymorphisms (SNPs). Samples with call rate < 0.98 and Pi hat > 0.375 by identity by descent test were excluded. SNPs with call rate < 0.97, minor allele frequency < 0.01, and the Hardy-Weinberg equilibrium P<0.00001 were excluded from the analysis. Association analyses were carried out under an additive model with adjustment for age and sex. We performed a meta-analysis of the two breeds using an inversed variance-weighted fixed effect model. All statistical analyses were performed using the SNP & Variation Suite software. Pathway analysis using ConsensusPathDB was performed for the loci with associations that exceeded P<0.0001.
Results :
After quality control, association analysis was performed on 114,040 SNPs in 102 Shiba-Inus (38 cases, 64 controls) and 48 Shih-Tzus (16 cases, 32 controls). Meta-analysis of two breeds identified 12 regions with P<0.0001 (ADGRG5-DOK4, ANK1-KAT6A, ZDHHC14-TMEM242, DEXI-OSER1, LARGE1, SLC4A10-DPP4, TDG-HSP90B1, TMEM108-CDV3, CKAP4-NUAK1, and 3 non-coding RNA loci). The strongest association was observed in rs22289342 in a non-coding RNA on chromosome 14 (P=9.13×10-6). Pathway analysis of the 12 suggestive regions revealed four pathways, including post-translational protein phosphorylation, regulation of insulin-like growth factor (IGF) transport/uptake by IGF binding proteins, post-translational protein modification, and epigenetic regulation of gene expression.
Conclusions :
This GWAS of canine glaucoma in two breeds identified several suggestive loci. Gene expression, transcription, and RNA processing were implicated in the pathogenesis of canine glaucoma.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.