Genetics

This scientific blog post examines a 2025 Scientific Reports study (Turk et al.) that leverages whole-exome sequencing to test whether rare, predicted pathogenic variants in genes previously highlighted by MS GWAS are enriched in familial multiple sclerosis (FMS) compared with sporadic MS and large population controls. Using stringent rarity and in silico pathogenicity filters and gene-burden modeling, the study reports a strong excess of such variants in FMS—but not in sporadic cases—implicating a small set of genes (including MALT1) as key contributors to familial risk. The post contextualizes these findings within the broader “missing heritability” problem, explains the analytic framework, and discusses biological plausibility, methodological constraints, and the implications for future family-based genetic studies and mechanistic validation.