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January 2023; 10 (1) Research ArticleOpen Access

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis

Eleni S. Vasileiou, Chen Hu, Charles N. Bernstein, Fred Lublin, Jerry S. Wolinsky, Gary R. Cutter, Elias S. Sotirchos, Kaarina Kowalec, Amber Salter, Shiv Saidha, Ellen M. Mowry, Peter A. Calabresi, Ruth Ann Marrie, Kathryn C. Fitzgerald
First published November 23, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200062
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Figures

  • Figure 1
    Figure 1 Decile of 25(OH)D PGS and Measured 25(OH)D Levels in 935 People With MS From the JHU Cohort

    25(OH)D PGS are derived from summary statistics in which the primary model was adjusted for BMI. The association between circulating 25(OH)D levels and 25(OH)D PGS are adjusted for also BMI among people with MS. We excluded individuals with measured levels exceeding 70 ng/mL, as previous studies suggest this threshold may be the physiologic limit of 25(OH)D derived from nonsupplemental sources. Similar results were obtained when applying a threshold of 100 ng/mL (not shown). 25[OH]D = 25-hydroxyvitamin D; PGS = polygenic score.

  • Figure 2
    Figure 2 Results for Continuous 25(OH)D PGS1 Clinical Outcomes for Individual Studies and the Pooled Estimate2 Across Studies

    125(OH)D PGS are derived from summary statistics in which the primary model was adjusted for BMI. 2Effect estimates displayed are for a 1 SD increase in 25(OH)D PGS. They are adjusted for age, 5 ancestry PCs, MS DMT, disease duration, and the number of relapses in previous 3 years. The pooled effect estimate is results from a random effects meta-analysis. (A) The results for rate of EDSS progression (heterogeneity I2 = 0.00%; p het=0.45). (B) The results for annualized percent change T25FW (I2 = 0.0%; p het=0.91). (C) The results for annualized percent change 9HPT (I2 = 0.0%; p het=0.67). 25[OH]D = 25-hydroxyvitamin D; 9HPT = nine-hole peg test; EDSS = expanded disability status scale; PGS = polygenic score; T25FW = timed 25-foot walk; DMT = disease-modifying therapies; JHU = Johns Hopkins; IMID = immune-mediated inflammatory diseases.

  • Figure 3
    Figure 3 Results for Continuous 25(OH)D PGS1 and MRI Outcomes for Individual Studies and the Pooled Estimate2 Across Studies

    125(OH)D PGS are derived from summary statistics in which the primary model was adjusted for BMI. 2Effect estimates displayed are for a 1 SD increase in 25(OH)D PGS. 2Effect estimates displayed are for a 1 SD increase in 25(OH)D PGS. They are adjusted for age, 5 ancestry PCs, MS DMT, disease duration, and the number of relapses in previous 3 years. The pooled effect estimate is results from a random effects meta-analysis. (A) The results for annualized percent change in BPF (Heterogeneity I2 = 66.0%; p het=0.09). (B) The results for annualized percent change in lesion volume (I2 = 0.0%; p het=0.78). (C) Relative rate for new lesions (I2 = 38.8%; p het=0.20). 25[OH]D = 25-hydroxyvitamin D; BPF = brain parenchymal fraction; DMT = disease-modifying therapies; JHU = Johns Hopkins; PGS = polygenic score.

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