Genetics

This article examines whether common genetic polymorphisms associated with serum lipid traits and body mass index (BMI) influence five-year disability accumulation in multiple sclerosis, quantified by annualised change in the Expanded Disability Status Scale (ΔEDSS). Using a longitudinal MS cohort with baseline lipid/BMI measurements and genome-wide genotyping, the authors identify several lipid-associated variants nominally linked to disability change and demonstrate that an aggregate lipid cumulative genetic risk score (CGRS) shows a pronounced dose–response relationship with ΔEDSS. Crucially, they report statistically significant interactions indicating that low HDL and an elevated total cholesterol:HDL ratio are most strongly associated with faster disability progression among individuals with higher lipid genetic risk, suggesting a gene–environment synergy that may help explain heterogeneity in clinical trajectories and responses to lipid-modifying interventions.