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

Abstract Subject headings

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.

By the author/editor: Loginovic, Pavel; Wang, Feiyi; Li, Jiang; Ferrat, Lauric; Mirshahi, Uyenli ...; Rao, H. Shanker; show more...; Petzold, Axel; Tyrrell, Jessica; Green, Harry D.; Weedon, Michael ...; Ganna, Andrea; Tuomi, Tiinamaij ...; Carey, David J.; Oram, Richard A.; Braithwaite, Tas ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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