Genetics

Multiple sclerosis is often described as a “genetic” disease—yet translating that idea into something clinically predictive is far from straightforward. This post walks through an unusual, tightly characterized family in which four siblings (including monozygotic triplets) developed MS, creating a rare opportunity to test whether a weighted genetic risk score built from known MS risk loci can explain familial clustering. The surprising outcome is that the highest score appears in an unaffected parent, while the affected siblings do not stand out genetically by this metric, pointing to the limits of common-variant polygenic prediction. We then explore how structural genomic signals—particularly a large region of loss of heterozygosity on chromosome 15 and candidate genes tied to myelin regulation and lipid metabolism—suggest alternative genetic architectures and biologically plausible pathways that may matter more in certain families than standard GWAS-based scoring.