Genetics

This blog post critically examines the current evidence linking genetic and epigenetic variation to clinical phenotype and disease severity in multiple sclerosis (MS), based on a comprehensive review by Jokubaitis and colleagues. While genetic studies have successfully elucidated the polygenic architecture of MS susceptibility, their translation into predictors of relapse activity and disability progression has proven far more challenging. The article explores why methodological constraints, imperfect severity metrics, and confounding environmental and treatment factors have limited progress, and highlights key advances—most notably the validated association between LRP2 variation and relapse risk—as proof that genetic modifiers of disease course do exist. It further discusses emerging roles for epigenetics, gene–environment interactions, and integrative genomic approaches as essential components of future precision medicine strategies in MS.