Investigation of the Association Between Polygenic Risk Scores and Brain MRI Metrics in Multiple Sclerosis Using a Large-Scale Database [Presidential Award Proceedings]

This study investigated the associations between multiple sclerosis polygenic risk scores (MS-PRS), white matter microstructural metrics derived from diffusion tensor Imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), and cognitive function using a large population-based dataset. MS-PRS was significantly associated with both DTI and NODDI metrics and cognitive function. Mediation analysis further revealed that white matter microstructural changes partially mediated the relationship between MS-PRS and cognitive decline, with mediation effects ranging from 1.6% to 5.4%. These findings suggest that genetic risk may contribute to cognitive impairment through its impact on white matter integrity.