Genetics

This blog post critically examines a large multicenter genetic study that tested whether established multiple sclerosis (MS) susceptibility loci—52 replicated GWAS risk variants, including aggregated polygenic risk scores—also predict clinical severity as quantified by the Multiple Sclerosis Severity Score (MSSS) in 7,125 individuals from 10 cohorts. The analysis finds that the cumulative burden of known MS risk alleles does not meaningfully associate with disability severity once relevant clinical covariates and disease-duration considerations are accounted for, and that nominal single-variant signals do not survive multiple-testing correction. By contrasting robust genetics of susceptibility with the elusive genetics of progression, the post highlights methodological challenges in severity phenotyping and outlines why future progress likely depends on larger prospective datasets, longitudinal endpoints, and biologically proximal measures such as quantitative MRI and treatment-aware models.