Genetics

This post covers Noroozi and colleagues' 2026 medRxiv preprint, a layered Mendelian randomization study testing 1,091 plasma metabolites and 309 ratios against the age-related MS severity score in 12,584 patients. It follows the design through each narrowing layer: instrument selection and the sensitivity battery, multivariable analysis that sharpens the lipid signal around arachidonate and betaine, colocalization at the chromosome 11 FADS locus and what the authors say it cannot separate, the miR-149-5p functional variant used to proxy FADS1 perturbation, cis-MR across seven brain cell types, and the CYP4F2 locus, closing on the subgroup hypothesis and the authors' own stated limitations.