Evidence for a causal relationship between low Vitamin D, high BMI, and pediatric-onset MS

Milena A. Gianfrancesco, Pernilla Stridh, Brooke Rhead, Xiaorong Shao, Edison Xu, Jennifer S. Graves, Tanuja Chitnis, Amy Waldman, Timothy Lotze, Teri Schreiner, Anita Belman, Benjamin Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan M. Tillema, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer RubinMeghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Soe Mar, Ilana Kahn, John Rose, Shelly Roalstad, T. Charles Casper, Ling Shen, Hong Quach, Diana Quach, Jan Hillert, Maria Bäärnhielm, Anna Hedstrom, Tomas Olsson, Ingrid Kockum, Lars Alfredsson, Catherine Metayer, Catherine Schaefer, Lisa F. Barcellos, Emmanuelle Waubant

Research output: Contribution to journalArticle

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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 5 394 cases, 10,875 controls) and Sweden (n 5 175 cases, 5,376 controls; total n 5 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 5 0.02) after controlling for sex, genetic ancestry, HLADRB1∗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 5 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.

Original languageEnglish (US)
Pages (from-to)1623-1629
Number of pages7
JournalNeurology
Volume88
Issue number17
DOIs
StatePublished - Apr 25 2017

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Gianfrancesco, M. A., Stridh, P., Rhead, B., Shao, X., Xu, E., Graves, J. S., Chitnis, T., Waldman, A., Lotze, T., Schreiner, T., Belman, A., Greenberg, B., Weinstock-Guttman, B., Aaen, G., Tillema, J. M., Hart, J., Caillier, S., Ness, J., Harris, Y., ... Waubant, E. (2017). Evidence for a causal relationship between low Vitamin D, high BMI, and pediatric-onset MS. Neurology, 88(17), 1623-1629. https://doi.org/10.1212/WNL.0000000000003849