Genetics

This article examines whether circulating levels of multiple sclerosis (MS)–related plasma proteins are substantially influenced by additive genetic factors and whether immune-focused genetic variation can explain that influence in practice. Using extended Sardinian pedigrees enriched for MS, the authors quantify narrow-sense heritability for 56 candidate proteins while explicitly modeling shared household environment, then conduct protein quantitative trait locus (pQTL) analyses using Immunochip genotypes in unaffected individuals to reduce disease-driven confounding. Their results identify a subset of proteins with moderate-to-high heritability and show that multi-SNP models drawn from Immunochip loci can explain a sizable fraction of variance for these proteins, supporting plasma protein traits as genetically regulated intermediate phenotypes with potential relevance for biomarker prioritization and mechanistic hypothesis generation in MS.