Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis
Eleni S. Vasileiou, Chen Hu, Çharles N. Bernstein, Fred Lublin, Jerry S. Wolinsky, Gary Cutter, Elias S. Sotirchos, Kaarina Kowalec, Amber Salter, Shiv Saidha, Ellen M. Mowry, Peter A. Calabresi, Ruth Ann Marrie, Kathryn C. Fitzgerald
Abstract
BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: ) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.