Metaanálisis2017
Evidence for a causal relationship between low vitamin D, high BMI, and pediatric-onset MS
Gianfrancesco MA, Stridh P, Rhead B, Shao X, Xu E, Graves JS, Chitnis T, Waldman A, Lotze T, Schreiner T, Belman A, Greenberg B, Weinstock-Guttman B, Aaen G, Tillema JM, Hart J, Caillier S, Ness J, Harris Y, Rubin J, Candee M, Krupp L, Gorman M, Benson L, Rodriguez M, Mar S, Kahn I, Rose J, Roalstad S, Casper TC, Shen L, Quach H, Quach D, Hillert J, Bäärnhielm M, Hedstrom A, Olsson T, Kockum I, Alfredsson L, Metayer C, Schaefer C, Barcellos LF, Waubant E, Network of Pediatric Multiple Sclerosis Centers
Neurology · 122 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institute on Aging
- Gobierno
- National Human Genome Research Institute
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- NINDS NIH HHS
- Gobierno
- NIA NIH HHS
- Gobierno
- NHGRI NIH HHS
- Subvenciones
- National Human Genome Research Institute (T32 HG 000047); National Institute of Neurological Disorders and Stroke (F31NS093832); National Institute of Neurological Disorders and Stroke (F31NS096885); National Institute of Neurological Disorders and Stroke (R01NS049510); National Institute of Neurological Disorders and Stroke (R01NS071463); National Institute on Aging (RC2 AG036607); National Institute of Neurological Disorders and Stroke (K23NS069806)
Según 6 financiadores declarados.
Publicación
- Publicado
- 2017-03-30 · Neurology · vol. 88 · número 17 · págs. 1623–1629
- Editorial
- Lippincott Williams & Wilkins
- Citado
- 168 citas · más que el 99% de estudios similares · 14.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 42 trabajos
- Acceso
- Acceso abierto (copia en repositorio)
- Áreas de investigación
- Multiple Sclerosis Research Studies · Vitamin D Research Studies · Genetic Associations and Epidemiology
- Palabras clave
- pediatric multiple sclerosis, vitamin D, 25-hydroxyvitamin D, body mass index, obesity, polygenic risk score, Mendelian randomization, causal relationship, disease susceptibility, HLA-DRB1*1501
- MeSH
- humans, multiple sclerosis, genetic predisposition to disease, vitamin d, body mass index, risk, age of onset, adolescent, united states, sweden, female, male, mendelian randomization analysis, hla-drb1 chains, biomarkers, white people
69 autores
- Milena A. Gianfrancesco🇺🇸🇸🇪Northwestern University; Boston Children's Hospital; St. Louis Children's Hospital; Primary Children's Hospital; State University of New York; Mayo Clinic; Karolinska University Hospital; Children's Hospital of Philadelphia; Children's National; Kaiser Permanente; University of Alabama; University of California, San Francisco; Baylor College of Medicine; Washington University in St. Louis; University of Utah; Kaiser Permanente Oakland Medical Center; Region Stockholm; Karolinska Institutet; University of Alabama at Birmingham; Massachusetts General Hospital; Children's Hospital Colorado; Stony Brook Medicine; Stony Brook Children's Hospital; Loma Linda University Children's Hospital; University at Buffalo, State University of New York; The University of Texas Southwestern Medical Center; University of Colorado Denver; University of California, Berkeley
- Pernilla Stridh🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Brooke Rhead🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Xiaorong Shao🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Edison Xu🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jennifer S. Graves🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Tanuja Chitnis🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Amy Tara Waldman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Timothy Edward Lotze🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Teri Schreiner🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Anita Lesgold Belman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Benjamin M. Greenberg🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Bianca Weinstock‐Guttman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Gregory Scott Aaen🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jan Mendelt Tillema🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Janace Hart🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Stacy J. Caillier🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jayne Ness🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Yolanda Harris🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jennifer P. Rubin🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Meghan S. Candee🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Lauren Krupp🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Mark Gorman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Leslie Benson🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Moses Rodriguez🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Soe Mar🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Ilana L. Kahn🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- JOHN W. ROSE🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Shelly Roalstad🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Theron Charles Casper🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Ling Shen🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Hong Quach🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Diana L. Quach🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jan A. Hillert🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Maria Bäärnhielm🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Anna Karin Hedström🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Tomas P Olsson🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Ingrid Skelton Kockum🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Lars S. Alfredsson🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Catherine Metayer🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Catherine A. Schaefer🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Lisa F. Barcellos🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Emmanuelle L. Waubant🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jennifer S. Graves🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Tanuja Chitnis🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Amy Tara Waldman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Timothy Loetze
- Teri Schreiner🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Anita Lesgold Belman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Benjamin M. Greenberg🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Bianca Weinstock‐Guttman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Gregory Scott Aaen🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jan Mendelt Tillema🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Janace Hart🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Stacy J. Caillier🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jayne Ness🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Yolanda Harris🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Jennifer P. Rubin🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Meghan S. Candee🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Lauren Krupp🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Mark Gorman🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Leslie Benson🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Moses Rodriguez🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Soe Mar🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Ilana L. Kahn🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- JOHN W. ROSE🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Shelly Roalstad🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Theron Charles Casper🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
- Emmanuelle L. Waubant🇸🇪🇺🇸Karolinska University Hospital; Karolinska Institutet; University of California, Berkeley
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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