Genetics

This blog post critically examines Almramhi et al. (2023), which applies two-sample Mendelian randomization to evaluate whether plasma lipid fractions and statin-mimicked molecular pathways exert causal effects on multiple sclerosis (MS) risk and severity. Leveraging large-scale GWAS and blood cis-eQTL resources, the study finds no genetic evidence that LDL-cholesterol or triglycerides causally influence MS susceptibility, while genetically predicted higher HDL-cholesterol associates with increased MS risk. Importantly, the analysis highlights a cholesterol-independent signal implicating the Rho GTPase gene RAC2 as potentially protective for MS risk, supporting the hypothesis that any statin-related effects in MS may arise from immunobiological mechanisms beyond cholesterol lowering.