Evidence mapPaperPMID 41533905Full record

ArticleInvestigative ophthalmology & visual science2026

Genetic Link Across Species: SIX6, a Major Human Glaucoma Gene, Confers Susceptibility to Glaucoma in Shiba-Inu Dogs.

Satoko Baba, Akira Meguro, Nobuyuki Kanemaki, Aoi Maeda, Hiroki Takahashi, Masaki Takeuchi, Lisa Endo, Eiichi Nomura, Jutaro Nakamura, Yuki Mizuki and 4 more

Abstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Satoko BabaDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Akira MeguroDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Nobuyuki KanemakiSchool of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
Aoi MaedaDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Hiroki TakahashiLaboratory of Small Animal Clinics, School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa, Japan.
Masaki TakeuchiDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Lisa EndoDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Eiichi NomuraDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Jutaro NakamuraDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Yuki MizukiDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Shun KanasashiDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Takuto SakonoDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Norihiro YamadaDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Nobuhisa MizukiDepartment of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: The SIX6 gene is a major susceptibility gene for human glaucoma, and its variants have been implicated in structural and functional alterations of the retina, such as nerve fiber layer thinning and retinal ganglion cell degeneration, which contribute to glaucoma development. This study investigated whether SIX6 polymorphisms are associated with glaucoma in dogs, focusing on the Shiba-Inu and Shih-Tzu breeds. Methods: We genotyped 19 single nucleotide polymorphisms within the SIX6 gene region in 109 Shiba-Inus (49 cases and 60 controls) and 57 Shih-Tzus (18 cases and 39 controls), followed by association analyses. Comparative sequence analysis of canine and human SIX6 was performed to assess evolutionary conservation. Results: In Shiba-Inus, rs851962234, located in the 3'-untranslated region of SIX6, was significantly associated with glaucoma (P = 0.0047; Pc = 0.038), with the minor A allele showing a frequency of 17.3% in cases and 4.2% in controls, and conferring an increased risk (odds ratio, 3.56). In contrast, rs851962234 showed no association in Shih-Tzus, likely owing to the rarity of the A allele in this breed. No other single nucleotide polymorphisms were associated with glaucoma in either breed. A comparative analysis showed a 98.4% amino acid identity between canine and human SIX6 across the coding regions. Conclusions: This study identifies rs851962234 in canine SIX6 as being significantly associated with glaucoma in Shiba-Inus, suggesting its potential role in modulating SIX6 expression and retinal ganglion cell vulnerability. These findings offer new insight into the genetic basis of canine glaucoma and highlight parallels and distinctions with human disease.

Indexed as

Dog DiseasesGenetic Predisposition to DiseaseGlaucomaHomeodomain ProteinsPolymorphism, Single NucleotideAnimalsDogsFemaleGene FrequencyGenotypeHumansTrans-ActivatorsHomeodomain ProteinsSIX6 protein, humanTrans-Activators

Identifiers

PMID41533905
PMCPMC12786397

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.