The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple Sclerosis Article Swipe
Gabriel Bsteh
,
Ruchi Tanavade
,
Nik Krajnc
,
Fabian Föttinger
,
Theresa König
,
Martin Krenn
,
Lukas Haider
,
Barbara Kornek
,
Fritz Leutmezer
,
Kerstin U. Ludwig
,
Stefan Macher
,
Tobias Monschein
,
Markus Ponleitner
,
Paulus Rommer
,
Christiane Schmied
,
Karin Zebenholzer
,
Tobias Zrzavy
,
Gudrun Zulehner
,
Franziska Di Pauli
,
Axel Schmidt
,
Harald Hegen
,
Berthold Pemp
,
Thomas Berger
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/acn3.70157
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/acn3.70157
Objective To investigate whether the rs10191329 risk allele in the DYSF–ZNF638 locus, which is implicated in central nervous system resilience rather than immune‐mediated pathology, is associated with retinal layer thinning, a biomarker of neuroaxonal damage in relapsing multiple sclerosis (RMS). Methods From a prospective observational study, we included RMS patients with ≥ 2 optical coherence tomography (OCT) scans, excluding eyes with optic neuritis during the observation period. DNA samples were genotyped using the Illumina Infinium Global Screening Array‐24 and variants imputed using the Haplotype Reference Consortium panel and Minimac4. Multivariable linear regression models were used to assess the association between rs10191329 risk allele number (rs10191329*A) and annualized rates of peripapillary retinal nerve fiber layer (aLpRNFL) and macular ganglion‐cell‐and‐inner‐plexiform‐layer (aLGCIPL) atrophy, adjusting for age, sex, MS‐specific variables, and 10 ancestry components. Results We included 183 RMS patients (mean age 35.9 years [SD 9.6], 74.9% female, median EDSS 2.0 [range 0–6.5], median observation 25 months [12–73], median OCT scans 3 [2–5]). Multivariable analyses revealed that each rs10191329*A allele was associated with a 0.10%/year increase in aLpRNFL (95% confidence interval [CI] 0.05–0.19, p < 0.001) and a 0.11%/year increase in aLGCIPL (95% CI 0.07–0.19, p < 0.001). The rs10191329 variant explained 8.9% of GCIPL atrophy and 8.2% of pRNFL atrophy variance. Interpretation Carriers of the rs10191329 risk allele show accelerated retinal atrophy, suggesting heightened neuroaxonal vulnerability in MS. While clinical implications are currently unclear, genetic stratification may be reasonable in clinical trials targeting neuroprotection.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/acn3.70157
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acn3.70157
- OA Status
- gold
- Cited By
- 1
- References
- 40
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412998333
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- OpenAlex ID
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https://openalex.org/W4412998333Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/acn3.70157Digital Object Identifier
- Title
-
The rs10191329 Risk Allele Is Associated With Pronounced Retinal Layer Atrophy in Multiple SclerosisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-08-04Full publication date if available
- Authors
-
Gabriel Bsteh, Ruchi Tanavade, Nik Krajnc, Fabian Föttinger, Theresa König, Martin Krenn, Lukas Haider, Barbara Kornek, Fritz Leutmezer, Kerstin U. Ludwig, Stefan Macher, Tobias Monschein, Markus Ponleitner, Paulus Rommer, Christiane Schmied, Karin Zebenholzer, Tobias Zrzavy, Gudrun Zulehner, Franziska Di Pauli, Axel Schmidt, Harald Hegen, Berthold Pemp, Thomas BergerList of authors in order
- Landing page
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https://doi.org/10.1002/acn3.70157Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acn3.70157Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acn3.70157Direct OA link when available
- Concepts
-
Medicine, Optic neuritis, Nerve fiber layer, Atrophy, Multiple sclerosis, Retinal, Confidence interval, Ophthalmology, Internal medicine, Optic nerve, Pathology, ImmunologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2025: 1Per-year citation counts (last 5 years)
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40Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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