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

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.

Wang, FeiyiUniversity of Helsinki (author)
Li, JiangSigfried and Janet Weis Center for Research (author)
Ferrat, LauricUniversity of Exeter (author)
Mirshahi, Uyenlinh L.Sigfried and Janet Weis Center for Research (author)
Rao, H. ShankerSigfried and Janet Weis Center for Research (author)
Petzold, AxelUniversity College London (author)
Tyrrell, JessicaUniversity of Exeter (author)
Green, Harry D.University of Exeter (author)
Weedon, Michael N.University of Exeter (author)
Ganna, AndreaMassachusetts General Hospital,University of Helsinki (author)
Tuomi, TiinamaijaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Folkhälsan Research Center,University of Helsinki(Swepub:lu)ti8736tu (author)
Carey, David J.Sigfried and Janet Weis Center for Research (author)
Oram, Richard A.University of Exeter (author)
Braithwaite, TasaneeKing's College London,St Thomas' Hospital (author)
University of ExeterUniversity of Helsinki (creator_code:org_t)
UKBB Eye & Vision Consortium
FinnGen
Geisinger-Regeneron DiscovEHR Collaboration

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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