Meta-Analysis

. 2017 Apr 25;88(17):1623-1629.

doi: 10.1212/WNL.0000000000003849. Epub 2017 Mar 29.

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

Milena A Gianfrancesco¹, Pernilla Stridh¹, Brooke Rhead¹, Xiaorong Shao¹, Edison Xu¹, Jennifer S Graves¹, Tanuja Chitnis¹, Amy Waldman¹, Timothy Lotze¹, Teri Schreiner¹, Anita Belman¹, Benjamin Greenberg¹, Bianca Weinstock-Guttman¹, Gregory Aaen¹, Jan M Tillema¹, Janace Hart¹, Stacy Caillier¹, Jayne Ness¹, Yolanda Harris¹, Jennifer Rubin¹, Meghan Candee¹, Lauren Krupp¹, Mark Gorman¹, Leslie Benson¹, Moses Rodriguez¹, Soe Mar¹, Ilana Kahn¹, John Rose¹, Shelly Roalstad¹, T Charles Casper¹, Ling Shen¹, Hong Quach¹, Diana Quach¹, Jan Hillert¹, Maria Bäärnhielm¹, Anna Hedstrom¹, Tomas Olsson¹, Ingrid Kockum¹, Lars Alfredsson¹, Catherine Metayer¹, Catherine Schaefer¹, Lisa F Barcellos¹, Emmanuelle Waubant²; Network of Pediatric Multiple Sclerosis Centers

Collaborators, Affiliations

Collaborators

Network of Pediatric Multiple Sclerosis Centers:
Jennifer Graves, Tanuja Chitnis, Amy Waldman, Timothy Loetze, Teri Schreiner, Anita Belman, Benjamin Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan M Tillema, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer Rubin, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Soe Mar, Ilana Kahn, John Rose, Shelly Roalstad, T Charles Casper, Emmanuelle Waubant

Affiliations

¹ From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA.
² From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA. emmanuelle.waubant@ucsf.edu.

PMID: 28356466
PMCID: PMC5405763
DOI: 10.1212/WNL.0000000000003849

Meta-Analysis

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

Milena A Gianfrancesco et al. Neurology. 2017.

. 2017 Apr 25;88(17):1623-1629.

doi: 10.1212/WNL.0000000000003849. Epub 2017 Mar 29.

Authors

Collaborators

Network of Pediatric Multiple Sclerosis Centers:
Jennifer Graves, Tanuja Chitnis, Amy Waldman, Timothy Loetze, Teri Schreiner, Anita Belman, Benjamin Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan M Tillema, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer Rubin, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Soe Mar, Ilana Kahn, John Rose, Shelly Roalstad, T Charles Casper, Emmanuelle Waubant

Affiliations

¹ From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA.
² From the Division of Epidemiology, School of Public Health (M.A.G., X.S., E.X., H.Q., D.Q., C.M., L.F.B.), and Computational Biology Graduate Group (B.R.), University of California, Berkeley; Department of Clinical Neuroscience and Center for Molecular Medicine (P.S.), Karolinska Institutet at Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (J.S.G., E.W.) and Regional Pediatric MS Center, Neurology (J.H., S.C.), University of California, San Francisco; Partners Pediatric Multiple Sclerosis Center (T.C.), Massachusetts General Hospital for Children, Boston; Division of Neurology (A.W.), Children's Hospital of Philadelphia, PA; Blue Bird Circle Multiple Sclerosis Center (T.L.), Baylor College of Medicine, Houston, TX; Children's Hospital Colorado (T.S.), University of Colorado, Denver; Lourie Center for Pediatric Multiple Sclerosis (A.B., L.K.), Stony Brook Children's Hospital, NY; Department of Neurology (B.G.), University of Texas Southwestern, Dallas; Pediatric Multiple Sclerosis Center (B.W.-G.), Jacobs Neurological Institute, SUNY Buffalo, NY; Pediatric MS Center at Loma Linda University Children's Hospital (G.A.), CA; Mayo Clinic's Pediatric Multiple Sclerosis Center (J.M.T., M.R.), Rochester, MN; University of Alabama Center for Pediatric-onset Demyelinating Disease (J.N., Y.H.), Children's Hospital of Alabama, Birmingham; Department of Pediatric Neurology (J.R.), Northwestern Feinberg School of Medicine, Chicago, IL; Primary Children's Hospital (M.C.), University of Utah, Salt Lake City; Boston Children's Hospital (M.G., L.B.), MA; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center (S.M.), St. Louis Children's Hospital, Washington University School of Medicine, MO; Children's National Medical Center (I.K.), Washington, DC; Departments of Neurology (J.R.) and Pediatrics (S.R., T.C.C.), University of Utah School of Medicine, Salt Lake City; Kaiser Permanente Division of Research (L.S., C.S., L.F.B.), Oakland, CA; Institute of Environmental Medicine (J.H., M.B., A.H., T.O., I.K., L.A.), Karolinska Institutet; Centre for Occupational and Environmental Medicine (L.A.), Stockholm County Council, Stockholm, Sweden; and Research Program on Genes, Environment and Health (C.S.), Kaiser Permanente, Oakland, CA. emmanuelle.waubant@ucsf.edu.

PMID: 28356466
PMCID: PMC5405763
DOI: 10.1212/WNL.0000000000003849

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.

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References

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials