| Title: | Timing and Predictive Value of Clinical Conditions Preceding Multiple Sclerosis in the UK Biobank |
| Journal: | Annals of Clinical and Translational Neurology |
| Published: | 26 Jun 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40574489/ |
| DOI: | https://doi.org/10.1002/acn3.70119 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/acn3.70119 |
Publication 16400
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Abstract
OBJECTIVES: Multiple sclerosis (MS) patients often experience a higher incidence of clinical conditions before diagnosis, suggesting a prodromal phase. However, their predictive value and temporal trajectories remain underexplored. We investigated these aspects using the large UK Biobank's population-based cohort, which provided clinical history through ICD-10 diagnosis codes.</p>
METHODS: We assessed associations between 600 clinical conditions and MS risk in 477,421 individuals using Cox models adjusted for demographics, smoking, and MS polygenic risk score (MS-PRS). Statistically significant conditions were included in a LASSO Cox regression (five-fold cross-validation on 70% training set) to identify key predictors, with performance assessed by the C-index and age-dependent area under the curve (AUC) in the 30% test set. Lastly, temporal trajectories of MS-associated conditions were analyzed in MS cases.</p>
RESULTS: We identified 192 conditions associated with MS, of which only ~20% were onset symptoms. Integrating these conditions into a predictive model already including demographics and smoking, improved the C-index from 0.65 to 0.71. Among the 30 model-selected best predictors, ~25% were prodromal conditions, including neuromuscular diseases, thromboembolism, and depression which typically occurred more than five years before MS diagnosis. Including MS-PRS further increased the C-index to 0.78, with an age-dependent AUC exceeding 0.80 in individuals over 50 years. Trajectory analysis highlighted migraine as a common early diagnosis, often followed by hypertension, depression, and dorsalgia.</p>
INTERPRETATION: Our findings highlight early conditions and diagnostic trajectories of MS, supporting the existence of a prodromal phase. These insights could improve MS prediction and facilitate earlier detection, particularly for late-onset cases.</p>
6 Authors
- Andrea Nova
- Teresa Fazia
- Giovanni Di Caprio
- Davide Gentilini
- Luisa Bernardinelli
- Roberto Bergamaschi
1 Application
| Application ID | Title |
|---|---|
| 93731 | Studying the impact of genetic variability, biochemical markers, environmental and lifestyle factors on Multiple Sclerosis onset risk and progression. |
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