Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis.

Humans Multiple Sclerosis / genetics Genome-Wide Association Study Vitamin D Brain Risk Factors

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
01 2023
Historique:
received: 17 07 2022
accepted: 26 09 2022
entrez: 23 11 2022
pubmed: 24 11 2022
medline: 26 11 2022
Statut: epublish

Résumé

Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10 Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

Sections du résumé

BACKGROUND AND OBJECTIVES
Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS.
METHODS
We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10
RESULTS
Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%;
DISCUSSION
Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.

Identifiants

DOI: 10.1212/NXI.0000000000200062 PMID: 36418179 PMC: PMC9747144
pubmed: 36418179
pii: 10/1/e200062
doi: 10.1212/NXI.0000000000200062
pmc: PMC9747144
pii:
doi:

Substances chimiques

Vitamin D 1406-16-2

Types de publication

Meta-Analysis Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIMH NIH HHS
ID : K01 MH121582
Pays : United States
Organisme : CIHR
ID : THC-135234
Pays : Canada

Informations de copyright

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Eleni S Vasileiou (ES)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0002-8639-8405

Chen Hu (C)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Charles N Bernstein (CN)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0001-8041-3574

Fred Lublin (F)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Jerry S Wolinsky (JS)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0002-8197-2762

Gary R Cutter (GR)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Elias S Sotirchos (ES)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0002-8812-1637

Kaarina Kowalec (K)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0003-3928-9879

Amber Salter (A)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0002-1088-110X

Shiv Saidha (S)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Ellen M Mowry (EM)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Peter A Calabresi (PA)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
ORCID: 0000-0002-7776-6472

Ruth Ann Marrie (RA)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Kathryn C Fitzgerald (KC)

From the Department of Neurology (E.S.V., C.H., E.S.S., S.S., E.M.M., P.A.C., K.C.F.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Internal Medicine (C.N.B.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Neurology (J.S.W.), McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth); Department of Biostatistics (G.R.C.), University of Alabama at Birmingham; College of Pharmacy (K.K.), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada; Department of Medical Epidemiology and Biostatistics (K.K.), Karolinska Institute, Solna, Sweden; Department of Neurology (A.S.), University of Texas Southwestern, Dallas; and Department of Community Health Sciences (R.A.M.), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada. fitzgerald@jhmi.edu.
ORCID: 0000-0003-3137-0322

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Association of Vitamin D Polygenic Risk Scores...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Association of Vitamin D Polygenic Risk Scores...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Association of Vitamin D Polygenic Risk Scores...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Sécostéroïdes › Vitamine D › Association of Vitamin D Polygenic Risk Scores...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Association of Vitamin D Polygenic Risk Scores...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Association of Vitamin D Polygenic Risk Scores...