Genetics

This blog post examines an Annals of Neurology study by Kreft and colleagues that rigorously tests whether a previously reported multiple sclerosis (MS) “severity” variant (rs10191329A) and related genetic risk score models can predict longitudinal disability and clinical milestones in an independent, prospectively followed registry cohort. Using standardized in-person EDSS assessments and age-related severity metrics, the investigators find no evidence that the proposed severity genotype—or susceptibility-based genetic burden—stratifies disability accumulation, relapse activity, or time to progression in real-world clinical settings. The post contextualizes these null results alongside modest replication of two suggestive severity variants and an age-at-onset association for an HLA-DRB1*1501 proxy, highlighting why independent replication, phenotype harmonization, and effect-size realism are essential before prognostic genotyping can be responsibly integrated into MS care.