Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis

Loginovic, Pavel ; Wang, Feiyi ; Li, Jiang ; Ferrat, Lauric ; Mirshahi, Uyenlinh L. ; Rao, H. Shanker ; Petzold, Axel ; Tyrrell, Jessica ; Green, Harry D. and Weedon, Michael N. , et al. (2024) In Nature Communications 15(1).
Abstract

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07–1.55, P < 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5–7%,... (More)

Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07–1.55, P < 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5–7%, lowest risk quartile) to 41% (95%CI 33–49%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
1415
publisher
Nature Publishing Group
external identifiers
  • pmid:38418465
  • scopus:85186240086
ISSN
2041-1723
DOI
10.1038/s41467-024-44917-9
language
English
LU publication?
yes
id
e8d6568a-772b-44e2-bb91-adfdbd92b257
date added to LUP
2024-03-14 14:53:13
date last changed
2025-05-09 23:41:45
@article{e8d6568a-772b-44e2-bb91-adfdbd92b257,
  abstract     = {{<p>Optic neuritis (ON) is associated with numerous immune-mediated inflammatory diseases, but 50% patients are ultimately diagnosed with multiple sclerosis (MS). Differentiating MS-ON from non-MS-ON acutely is challenging but important; non-MS ON often requires urgent immunosuppression to preserve vision. Using data from the United Kingdom Biobank we showed that combining an MS-genetic risk score (GRS) with demographic risk factors (age, sex) significantly improved MS prediction in undifferentiated ON; one standard deviation of MS-GRS increased the Hazard of MS 1.3-fold (95% confidence interval 1.07–1.55, P &lt; 0.01). Participants stratified into quartiles of predicted risk developed incident MS at rates varying from 4% (95%CI 0.5–7%, lowest risk quartile) to 41% (95%CI 33–49%, highest risk quartile). The model replicated across two cohorts (Geisinger, USA, and FinnGen, Finland). This study indicates that a combined model might enhance individual MS risk stratification, paving the way for precision-based ON treatment and earlier MS disease-modifying therapy.</p>}},
  author       = {{Loginovic, Pavel and Wang, Feiyi and Li, Jiang and Ferrat, Lauric and Mirshahi, Uyenlinh L. and Rao, H. Shanker and Petzold, Axel and Tyrrell, Jessica and Green, Harry D. and Weedon, Michael N. and Ganna, Andrea and Tuomi, Tiinamaija and Carey, David J. and Oram, Richard A. and Braithwaite, Tasanee}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Applying a genetic risk score model to enhance prediction of future multiple sclerosis diagnosis at first presentation with optic neuritis}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-44917-9}},
  doi          = {{10.1038/s41467-024-44917-9}},
  volume       = {{15}},
  year         = {{2024}},
}