Author:
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,
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
138 articles.
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