Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS. (25th April 2017)

• Record Type: Journal Article
• Authors: Gianfrancesco, Milena A.; Stridh, Pernilla; Rhead, Brooke; Shao, Xiaorong; Xu, Edison; Graves, Jennifer S.; Chitnis, Tanuja; Waldman, Amy; Lotze, Timothy; Schreiner, Teri; Belman, Anita; Greenberg, Benjamin; Weinstock-Guttman, Bianca; Aaen, Gregory; Tillema, Jan M.; Hart, Janace; Caillier, Stacy; Ness, Jayne; Harris, Yolanda; Rubin, Jennifer; Candee, Meghan; Krupp, Lauren; Gorman, Mark; Benson, Leslie; Rodriguez, Moses; Mar, Soe; Kahn, Ilana; Rose, John; Roalstad, Shelly; Casper, T. Charles; Shen, Ling; Quach, Hong; Quach, Diana; Hillert, Jan; Bäärnhielm, Maria; Hedstrom, Anna; Olsson, Tomas; Kockum, Ingrid; Alfredsson, Lars; Metayer, Catherine; Schaefer, Catherine; Barcellos, Lisa F.; Waubant, Emmanuelle;
• Is Part Of: Neurology. Volume 88:Number 17(2017)
• Publication Date: 2017-04-25
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000003849
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic variants associated with levels of 25(OH)D in serum using the estimated effect of each risk variant. A BMI GRS was also created that incorporates the cumulative effect of 97 variants associated with BMI. Participants included non-Hispanic white individuals recruited from over 15 sites across the United States (n = 394 cases, 10, 875 controls) and Sweden (n = 175 cases, 5, 376 controls; total n = 16, 820). Results: Meta-analysis findings demonstrated that a vitD GRS associated with increasing levels of 25(OH)D in serum decreased the odds of pediatric-onset MS (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.55, 0.94; p = 0.02) after controlling for sex, genetic ancestry, HLA-DRB1*15:01, and over 100 non–human leukocyte antigen MS risk variants. A significant association between BMI GRS and pediatric disease onset was also demonstrated (OR 1.17, 95% CI 1.05, 1.30; p = 0.01) after adjusting for covariates. Estimates for each GRS were unchanged when considered together in a multivariable model. Conclusions: We provide evidence supporting independent and causal effects of decreased vitamin D levels and increased BMI on susceptibility to pediatric-onset MS.